RANDY DEAN BLAKELY

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc Forward genetic analysis to identify determinants of dopamine signaling in Caenorhabditis elegans using swimming-induced paralysis
    J Andrew Hardaway
    Department of Pharmacology, and Silvio O Conte Center for Neuroscience Research, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    G3 (Bethesda) 2:961-75. 2012
  2. pmc Choline transporter gene variation is associated with attention-deficit hyperactivity disorder
    Brett A English
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232 8548, USA
    J Neurodev Disord 1:252-63. 2009
  3. pmc Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse
    Jeremy Veenstra-Vanderweele
    Departments of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    J Neurodev Disord 1:158-71. 2009
  4. pmc Subcellular localization of the antidepressant-sensitive norepinephrine transporter
    Heinrich J G Matthies
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    BMC Neurosci 10:65. 2009
  5. ncbi request reprint Biogenic amine neurotransmitter transporters: just when you thought you knew them
    Randy D Blakely
    Department of Pharmacology, Molecular Physiology and Biophysics, Vanderbilt School of Medicine, Nashville, TN, USA
    Physiology (Bethesda) 20:225-31. 2005
  6. ncbi request reprint All aglow about presynaptic receptor regulation of neurotransmitter transporters
    Randy D Blakely
    Department of Pharmacology, Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Mol Pharmacol 71:1206-8. 2007
  7. pmc cGMP-dependent protein kinase Ialpha associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake
    Jennifer A Steiner
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mol Brain 2:26. 2009
  8. ncbi request reprint A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6-hydroxydopamine identifies dopamine transporter mutants impacting transporter biosynthesis and trafficking
    Richard Nass
    Department of Anesthesiology, Vanderbilt School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurochem 94:774-85. 2005
  9. pmc Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
    Richard Nass
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 6420, USA
    Proc Natl Acad Sci U S A 99:3264-9. 2002
  10. pmc Hereditary spastic paraplegia-associated mutations in the NIPA1 gene and its Caenorhabditis elegans homolog trigger neural degeneration in vitro and in vivo through a gain-of-function mechanism
    Jiali Zhao
    Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232 8552, USA
    J Neurosci 28:13938-51. 2008

Research Grants

Detail Information

Publications79

  1. pmc Forward genetic analysis to identify determinants of dopamine signaling in Caenorhabditis elegans using swimming-induced paralysis
    J Andrew Hardaway
    Department of Pharmacology, and Silvio O Conte Center for Neuroscience Research, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    G3 (Bethesda) 2:961-75. 2012
    ..Our studies validate the utility of the Swip screen, demonstrate the functional relevance of DA transporter structural elements, and reveal novel genomic loci that encode regulators of DA signaling...
  2. pmc Choline transporter gene variation is associated with attention-deficit hyperactivity disorder
    Brett A English
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232 8548, USA
    J Neurodev Disord 1:252-63. 2009
    ..These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder...
  3. pmc Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse
    Jeremy Veenstra-Vanderweele
    Departments of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    J Neurodev Disord 1:158-71. 2009
    ..We discuss both the opportunities and challenges that await the physiological/behavioral analysis of Gly56Ala transgenic mice, with particular reference to modeling autism-associated traits...
  4. pmc Subcellular localization of the antidepressant-sensitive norepinephrine transporter
    Heinrich J G Matthies
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    BMC Neurosci 10:65. 2009
    ..Limited, and somewhat contradictory, information currently describes the axonal transport and localization of NET in neurons...
  5. ncbi request reprint Biogenic amine neurotransmitter transporters: just when you thought you knew them
    Randy D Blakely
    Department of Pharmacology, Molecular Physiology and Biophysics, Vanderbilt School of Medicine, Nashville, TN, USA
    Physiology (Bethesda) 20:225-31. 2005
    ....
  6. ncbi request reprint All aglow about presynaptic receptor regulation of neurotransmitter transporters
    Randy D Blakely
    Department of Pharmacology, Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Mol Pharmacol 71:1206-8. 2007
    ....
  7. pmc cGMP-dependent protein kinase Ialpha associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake
    Jennifer A Steiner
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Mol Brain 2:26. 2009
    ..PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear...
  8. ncbi request reprint A genetic screen in Caenorhabditis elegans for dopamine neuron insensitivity to 6-hydroxydopamine identifies dopamine transporter mutants impacting transporter biosynthesis and trafficking
    Richard Nass
    Department of Anesthesiology, Vanderbilt School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurochem 94:774-85. 2005
    ....
  9. pmc Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
    Richard Nass
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 6420, USA
    Proc Natl Acad Sci U S A 99:3264-9. 2002
    ..6-OHDA-triggered neural degeneration does not require the CED-3/CED-4 cell death pathway, but is abolished by the genetic disruption of the C. elegans DAT...
  10. pmc Hereditary spastic paraplegia-associated mutations in the NIPA1 gene and its Caenorhabditis elegans homolog trigger neural degeneration in vitro and in vivo through a gain-of-function mechanism
    Jiali Zhao
    Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232 8552, USA
    J Neurosci 28:13938-51. 2008
    ..We propose that HSP-associated mutations in NIPA1 lead to cellular and functional deficits through a gain-of-function mechanism supporting the ER accumulation of toxic NIPA1 proteins...
  11. ncbi request reprint Vesicular localization and activity-dependent trafficking of presynaptic choline transporters
    Shawn M Ferguson
    Neuroscience Graduate Program, Center for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Neurosci 23:9697-709. 2003
    ....
  12. ncbi request reprint The Caenorhabditis elegans choline transporter CHO-1 sustains acetylcholine synthesis and motor function in an activity-dependent manner
    Dawn Signor Matthies
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurosci 26:6200-12. 2006
    ..Our findings establish a requirement for presynaptic choline transport activity in vivo in a model amenable to a genetic dissection of CHO-1 regulation...
  13. ncbi request reprint A regulated interaction of syntaxin 1A with the antidepressant-sensitive norepinephrine transporter establishes catecholamine clearance capacity
    Uhna Sung
    Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurosci 23:1697-709. 2003
    ..These two contradictory roles of syntaxin 1A on NET appear to be linked and reveal a dynamic cycle of interactions that allow for the coordinated control between NE release and reuptake...
  14. ncbi request reprint Calcium-dependent inhibition of synaptosomal serotonin transport by the alpha 2-adrenoceptor agonist 5-bromo-N-[4,5-dihydro-1H-imidazol-2-yl]-6-quinoxalinamine (UK14304)
    Twum Ampofo Ansah
    Department of Pharmacology, Meharry Medical College, 1005 D B Todd Blvd, Nashville, TN 37208, USA
    J Pharmacol Exp Ther 305:956-65. 2003
    ..Our findings suggest that UK14304 modulates SERT function in vitro and in vivo via signaling pathways, possibly supported by an influx of Ca2+ through voltage-sensitive Ca2+ channels...
  15. pmc Anomalous dopamine release associated with a human dopamine transporter coding variant
    Michelle S Mazei-Robison
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 8548, USA
    J Neurosci 28:7040-6. 2008
    ..Additionally, they suggest that block of inappropriate neurotransmitter efflux may be an unsuspected mechanism supporting the therapeutic actions of existing transporter-directed medications...
  16. ncbi request reprint Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants
    L Keith Henry
    Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Biol Chem 281:2012-23. 2006
    ..These studies provided evidence for distinct binding sites coordinating SERT antagonists and revealed a close interaction between TM1 and TM3 differentially targeted by stereoisomers of CIT...
  17. ncbi request reprint Expression studies of naturally occurring human dopamine transporter variants identifies a novel state of transporter inactivation associated with Val382Ala
    Michelle S Mazei-Robison
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA
    Neuropharmacology 49:737-49. 2005
    ..Analysis of PMA-induced V382A internalization revealed a trafficking-independent action of PMA, consistent with the existence of a surface-localized, transport-inactive state...
  18. ncbi request reprint Sequence variation in the human dopamine transporter gene in children with attention deficit hyperactivity disorder
    Michelle S Mazei-Robison
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 8548, USA
    Neuropharmacology 49:724-36. 2005
    ..Interestingly, the A559V variant was previously identified in a subject with bipolar disorder [. Molecular Psychiatry 5, 275], a psychiatric disorder that has a significant number of overlapping symptoms with ADHD...
  19. ncbi request reprint Na+, Cl-, and pH dependence of the human choline transporter (hCHT) in Xenopus oocytes: the proton inactivation hypothesis of hCHT in synaptic vesicles
    Hideki Iwamoto
    Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurosci 26:9851-9. 2006
    ..This mechanism would allow cholinergic, activity-triggered delivery of silent choline transporters to the plasma membrane, in which normal pH would reactivate the transporters for choline uptake and subsequent acetylcholine synthesis...
  20. ncbi request reprint Adenosine receptor, protein kinase G, and p38 mitogen-activated protein kinase-dependent up-regulation of serotonin transporters involves both transporter trafficking and activation
    Chong Bin Zhu
    Department of Psychiatry, Vanderbilt School of Medicine, Nashville, Tennessee 37232 8548, USA
    Mol Pharmacol 65:1462-74. 2004
    ..Together, these results reveal two PKG-dependent pathways supporting rapid SERT regulation by A3 ARs, one leading to enhanced SERT surface trafficking, and a separate, p38 MAPK-dependent process augmenting SERT intrinsic activity...
  21. pmc Interactions between integrin alphaIIbbeta3 and the serotonin transporter regulate serotonin transport and platelet aggregation in mice and humans
    Ana Marin D Carneiro
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Clin Invest 118:1544-52. 2008
    ....
  22. ncbi request reprint Cell surface trafficking of the antidepressant-sensitive norepinephrine transporter revealed with an ectodomain antibody
    Valentina Savchenko
    Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Mol Cell Neurosci 24:1131-50. 2003
    ..These findings provide the first evidence for regulated trafficking of NET in neurons and support the suggestion that activity-dependent NET trafficking may provide additional modulatory capacity for noradrenergic signaling...
  23. ncbi request reprint Targeting cell surface receptors with ligand-conjugated nanocrystals
    Sandra J Rosenthal
    Department of Chemistry, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, Tennessee 37235, USA
    J Am Chem Soc 124:4586-94. 2002
    ..These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells...
  24. pmc Dopamine transporters depolarize neurons by a channel mechanism
    Lucia Carvelli
    Department of Pharmacology and Center of Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Proc Natl Acad Sci U S A 101:16046-51. 2004
    ..Thus, DA transporters not only transport DA but also exhibit a channel mode of conduction that directly modulates membrane potential and neuronal function...
  25. pmc Allelic heterogeneity at the serotonin transporter locus (SLC6A4) confers susceptibility to autism and rigid-compulsive behaviors
    James S Sutcliffe
    Center for Molecular Neuroscience, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232 0615, USA
    Am J Hum Genet 77:265-79. 2005
    ..In the aggregate, these variants show significant linkage to and association with autism. Our data provide strong support for a collection of multiple, often rare, alleles at SLC6A4 as imposing risk of autism...
  26. ncbi request reprint The Caenorhabditis elegans dopaminergic system: opportunities for insights into dopamine transport and neurodegeneration
    Richard Nass
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6420, USA
    Annu Rev Pharmacol Toxicol 43:521-44. 2003
    ..elegans with an eye toward opportunities for uncovering DAT mutants, DAT regulators, and components of toxin-mediated cell death...
  27. doi request reprint Bound to be different: neurotransmitter transporters meet their bacterial cousins
    L Keith Henry
    Department of Pharmacology, Vanderbilt University Nashville, TN 37232 8548, USA
    Mol Interv 7:306-9. 2007
    ....
  28. pmc Rab11 supports amphetamine-stimulated norepinephrine transporter trafficking
    Heinrich J G Matthies
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Neurosci 30:7863-77. 2010
    ..Our data demonstrate that AMPH leads to an increase of NET in endosomes of single boutons and varicosities in a Rab11-dependent manner...
  29. pmc Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission
    Lucia Carvelli
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Proc Natl Acad Sci U S A 105:14192-7. 2008
    ..We propose that loss of UNC-64/DAT-1 interactions leads to enhanced synaptic DA release, providing a novel mechanism for DA neuron sensitization that may be relevant to mechanisms of DA-associated disorders...
  30. ncbi request reprint The functional impact of SLC6 transporter genetic variation
    Maureen K Hahn
    Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Annu Rev Pharmacol Toxicol 47:401-41. 2007
    ..Refining phenotypes, through assessment of endophenotypes, specific behavioral tasks, medication response, and brain network properties has also improved detection of the impact of genetic variation on complex behavior and disease...
  31. pmc Amphetamine induces dopamine efflux through a dopamine transporter channel
    Kristopher M Kahlig
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 465 21st Avenue South, Nashville, TN 37232 8548, USA
    Proc Natl Acad Sci U S A 102:3495-500. 2005
    ..Unlike AMPH, the endogenous substrate DA, when present on both sides of the plasma membrane, inhibits this channel-like activity, thereby suggesting that the DAT channel-like mode cannot accumulate DA against a concentration gradient...
  32. ncbi request reprint High affinity inhibitors of the dopamine transporter (DAT): novel biotinylated ligands for conjugation to quantum dots
    Ian D Tomlinson
    The Department of Chemistry, Vanderbilt University, Nashville, TN 37235 1822, USA
    Bioorg Med Chem Lett 16:4664-7. 2006
    ..This letter describes the synthesis of biotinylated analogs of the DAT antagonists GBR 12909 and GBR 12935 that can be attached to streptavidin coated cadmium selenide/zinc sulfide/core shell nanocrystals...
  33. pmc Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes
    Ana M D Carneiro
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Proc Natl Acad Sci U S A 106:2047-52. 2009
    ..Our studies provide an example of the power of coordinated in vitro, in vivo, and in silico approaches using mouse RI lines to elucidate and quantify the system-level impact of gene variation...
  34. ncbi request reprint Binding and transport in norepinephrine transporters. Real-time, spatially resolved analysis in single cells using a fluorescent substrate
    Joel W Schwartz
    Department of Pharmacology, Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, Tennessee 37232 8548, USA
    J Biol Chem 278:9768-77. 2003
    ....
  35. ncbi request reprint Inhibitors of the serotonin transporter protein (SERT): the design and synthesis of biotinylated derivatives of 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indoles. High-affinity serotonergic ligands for conjugation with quantum dots
    Ian D Tomlinson
    The Department of Chemistry, Vanderbilt University, Station B, 351822, Nashville, TN 37235 1822, USA
    Bioorg Med Chem Lett 15:5307-10. 2005
    ..This letter describes the design and synthesis of two different biotinylated SERT antagonists that can be attached to streptavidin-coated cadmium selenide/zinc sulfide core shell nanocrystals...
  36. ncbi request reprint Vigorous motor activity in Caenorhabditis elegans requires efficient clearance of dopamine mediated by synaptic localization of the dopamine transporter DAT-1
    Paul W McDonald
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurosci 27:14216-27. 2007
    ..elegans are tightly regulated by synaptic DAT-1...
  37. pmc Enhanced activity of human serotonin transporter variants associated with autism
    Harish C Prasad
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Philos Trans R Soc Lond B Biol Sci 364:163-73. 2009
    ..When expressed stably from the same genomic locus in CHO cells, both Gly56Ala and Ile425Leu display catalytic activation, accompanied by a striking loss of SERT protein...
  38. ncbi request reprint Stimulation of serotonin transport by the cyclic GMP phosphodiesterase-5 inhibitor sildenafil
    Chong Bin Zhu
    Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Eur J Pharmacol 504:1-6. 2004
    ..These findings implicate cGMP-targeted PDEs in limiting the regulation of antidepressant-sensitive 5-HT transport...
  39. ncbi request reprint The choline transporter resurfaces: new roles for synaptic vesicles?
    Shawn M Ferguson
    Neuroscience Graduate Program, Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    Mol Interv 4:22-37. 2004
    ....
  40. ncbi request reprint p38 MAPK activation elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process
    Chong Bin Zhu
    Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Biol Chem 280:15649-58. 2005
    ....
  41. ncbi request reprint Synthesis and characterization of a pegylated derivative of 3-(1,2,3,6-tetrahydro-pyridin-4yl)-1H-indole (IDT199): a high affinity SERT ligand for conjugation to quantum dots
    Ian D Tomlinson
    The Department of Chemistry, Vanderbilt University, Station B, 351822, Nashville, TN 37235 1822, USA
    Bioorg Med Chem Lett 17:5656-60. 2007
    ..In this paper we report the design and synthesis of a ligand that has a high affinity for the serotonin transporter (SERT) that may be conjugated to quantum dots...
  42. ncbi request reprint Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis
    Regula E Egli
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 0615, USA
    Neuropsychopharmacology 30:657-68. 2005
    ..Further experiments demonstrate that the actions of NE on glutamatergic transmission can be correlated with beta-AR function...
  43. pmc Dysregulation of dopamine transporters via dopamine D2 autoreceptors triggers anomalous dopamine efflux associated with attention-deficit hyperactivity disorder
    Erica Bowton
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurosci 30:6048-57. 2010
    ..These studies identify a signaling network downstream of D(2)R activation, normally constraining DA action at synapses, that may be altered by DAT mutation to impact risk for DA-related disorders...
  44. pmc Structural determinants of species-selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies
    KRISTIAN W KAUFMANN
    Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235 1822, USA
    Proteins 74:630-42. 2009
    ..Our studies identify a number of potential contacts whose contribution to substrate binding and transport was previously unsuspected...
  45. pmc Going with the flow: trafficking-dependent and -independent regulation of serotonin transport
    Jennifer A Steiner
    Graduate Training Program in Neuroscience, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Traffic 9:1393-402. 2008
    ..Elucidation of the SERT 'regulome' provides important depth to our understanding of the likely origins of 5-HT-associated disorders and may help orient research to develop novel therapeutics...
  46. pmc Transmembrane domain 6 of the human serotonin transporter contributes to an aqueously accessible binding pocket for serotonin and the psychostimulant 3,4-methylene dioxymethamphetamine
    Julie R Field
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 8548, USA
    J Biol Chem 285:11270-80. 2010
    ..In the context of prior studies on TM1, our findings document shared and unique features of TM6 contributing to hSERT aqueous accessibility, ligand recognition, and conformational dynamics...
  47. ncbi request reprint Rapid stimulation of presynaptic serotonin transport by A(3) adenosine receptors
    Chong Bin Zhu
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Pharmacol Exp Ther 322:332-40. 2007
    ..Together, these results identify a novel, region-specific action of CNS A(3)ARs in the modulation of SERT-mediated 5-HT transport that may be relevant for the etiology and/or therapy of 5-HT-linked brain disorders...
  48. ncbi request reprint Desvenlafaxine succinate identifies novel antagonist binding determinants in the human norepinephrine transporter
    John N Mason
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    J Pharmacol Exp Ther 323:720-9. 2007
    ..In an initial search for molecular features that differentially define antagonist binding determinants, we document that Val148 in hNET transmembrane domain 3 selectively disrupts NIS binding but not that of DVS...
  49. ncbi request reprint The N-terminus of the norepinephrine transporter regulates the magnitude and selectivity of the transporter-associated leak current
    Francesca Binda
    Department of Molecular Physiology and Biophysics, Vanderbilt University, 465 21st Ave South, Nashville, TN 37232 8548, USA
    Neuropharmacology 50:354-61. 2006
    ..These data suggest that the NET N-terminus regulates and defines the ionic specificity of the NET-mediated leak current...
  50. pmc Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase
    Harish C Prasad
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Proc Natl Acad Sci U S A 102:11545-50. 2005
    ....
  51. ncbi request reprint Single nucleotide polymorphisms in the human norepinephrine transporter gene affect expression, trafficking, antidepressant interaction, and protein kinase C regulation
    Maureen K Hahn
    Center for Molecular Neuroscience, 6133 Medical Research Building III, Suite 7140, Vanderbilt School of Medicine, Nashville, TN 37232 8548, USA
    Mol Pharmacol 68:457-66. 2005
    ..These findings reveal functional deficits that are likely to compromise NE signaling in SNP carriers in the population and identify key regions of NET contributing to transporter biosynthesis, activity, and regulation...
  52. ncbi request reprint A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters
    Maureen K Hahn
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Neurosci 23:4470-8. 2003
    ..These results elucidate a molecular mechanism for the disrupted NE homeostasis and cardiovascular function evident in OI patients with the hNET-A457P mutation...
  53. pmc Lethal impairment of cholinergic neurotransmission in hemicholinium-3-sensitive choline transporter knockout mice
    Shawn M Ferguson
    Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 101:8762-7. 2004
    ..Our results demonstrate that CHT is an essential and regulated presynaptic component of cholinergic signaling and indicate that CHT warrants consideration as a candidate gene for disorders characterized by cholinergic hypofunction...
  54. pmc Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter
    Ana Marin D Carneiro
    Departments of Pharmacology and Psychiatry, Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    J Biol Chem 281:24769-80. 2006
    ..Associations of SERT with Hic-5 are evident in brain synaptosomes, suggesting the existence of parallel mechanisms operating to regulate SERT at serotonergic synapses...
  55. ncbi request reprint Dopamine signaling architecture in Caenorhabditis elegans
    Paul W McDonald
    Graduate Program in Neuroscience, Department of Pharmacology, Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 8548, USA
    Cell Mol Neurobiol 26:593-618. 2006
    ..1...
  56. ncbi request reprint Genetic basis of clinical catecholamine disorders
    Emily M Garland
    Department of Pharmacology, Autonomic Dysfunction Center, Department of Medicine, Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Ann N Y Acad Sci 971:506-14. 2002
    ....
  57. ncbi request reprint Labeling cell-surface proteins via antibody quantum dot streptavidin conjugates
    John N Mason
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
    Methods Mol Biol 303:35-50. 2005
    ..In this chapter, we outline the methodology for using streptavidin quantum dots to label biotinylated antibodies that target cell-surface ectodomain proteins on both living and fixed cells...
  58. doi request reprint Quantum dot ex vivo labeling of neuromuscular synapses
    Rebecca L Orndorff
    Department of Chemistry, Vanderbilt University, Vanderbilt School of Medicine, Vanderbilt University, Nashville, Tennessee 37235 1822, USA
    Nano Lett 8:780-5. 2008
    ..This approach provides a novel methodology for the direct assessment of the presence and mobility of neurotransmitter receptors in native tissue...
  59. pmc Calcium-dependent interactions of the human norepinephrine transporter with syntaxin 1A
    Uhna Sung
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 8548, USA
    Mol Cell Neurosci 34:251-60. 2007
    ..Furthermore, PMA enhanced Ca2+-dependent modulation of NE transport in synaptosomes. Our data reveal roles for SYN1A in the Ca2+-dependent regulation of NET, likely reliant on regulation by PKC signaling, but independent of CaMK...
  60. ncbi request reprint Localization of cholinergic innervation in guinea pig heart by immunohistochemistry for high-affinity choline transporters
    Donald B Hoover
    Department of Pharmacology, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
    Cardiovasc Res 62:112-21. 2004
    ..This study maps cholinergic innervation of guinea pig heart using a new antibody to the human high-affinity choline transporter (CHT), which is present only in cholinergic nerves...
  61. ncbi request reprint Amphetamine induces a calcium/calmodulin-dependent protein kinase II-dependent reduction in norepinephrine transporter surface expression linked to changes in syntaxin 1A/transporter complexes
    Concetta Dipace
    Department of Molecular Physiology and Biophysics, Center for Molecular Neuroscience, Vanderbilt University Medical Center, 465 21st Avenue South, 7124A Medical Research Building III, Nashville, TN 37232, USA
    Mol Pharmacol 71:230-9. 2007
    ..Here, we demonstrate that AMPH stimulation of CAMKII stabilizes an hNET/SYN1A complex. This hNET/SYN1A complex rapidly redistributes, upon AMPH treatment, when mechanisms supported by the transporter's NH2 terminus are eliminated...
  62. pmc Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine
    Jason M Williams
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    PLoS Biol 5:e274. 2007
    ..These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders...
  63. ncbi request reprint The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters
    Chong Bin Zhu
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232 8645, USA
    Neuropsychopharmacology 31:2121-31. 2006
    ..These results provide the first evidence that proinflammatory cytokines can acutely regulate neuronal SERT activity via p38 MAPK-linked pathways...
  64. pmc Colocalization and regulated physical association of presynaptic serotonin transporters with A₃ adenosine receptors
    Chong Bin Zhu
    Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Mol Pharmacol 80:458-65. 2011
    ....
  65. ncbi request reprint Peptide-conjugated quantum dots: imaging the angiotensin type 1 receptor in living cells
    Ian D Tomlinson
    Department of Chemistry, Vanderbilt University, Nashville, TN, USA
    Methods Mol Biol 303:51-60. 2005
    ..The Ang II-quantum dot conjugates did not bind to parental cells and showed similar staining patterns when compared with a commercially available Ang II Alexa 488 conjugate...
  66. ncbi request reprint Distinctions between dopamine transporter antagonists could be just around the bend
    L Keith Henry
    Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA
    Mol Pharmacol 73:616-8. 2008
    ....
  67. ncbi request reprint Getting the message across: a recent transporter structure shows the way
    L Keith Henry
    Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Neuron 49:791-6. 2006
    ....
  68. ncbi request reprint Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein
    Merja Lakso
    Department of Neurobiology, A I Virtanen Institute, Kuopio University, Finland
    J Neurochem 86:165-72. 2003
    ..This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies...
  69. ncbi request reprint 5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors
    Adamantios Serafeim
    MRC Centre for Immune Regulation and the Department of Pharmacology, Medical School, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK
    Blood 99:2545-53. 2002
    ..These data indicate that serotonin drives apoptosis in biopsylike BL cells after its entry through an active transport mechanism, and they suggest a novel therapeutic modality for Burkitt lymphoma...
  70. pmc A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder
    Chun Hyung Kim
    Molecular Neurobiology, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
    Proc Natl Acad Sci U S A 103:19164-9. 2006
    ....
  71. ncbi request reprint Evidence for biphasic effects of protein kinase C on serotonin transporter function, endocytosis, and phosphorylation
    Lankupalle D Jayanthi
    Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Ave, BSB 403, Charleston, SC 29425, USA
    Mol Pharmacol 67:2077-87. 2005
    ....
  72. doi request reprint Functional gene variation in the human norepinephrine transporter: association with attention deficit hyperactivity disorder
    Chun Hyung Kim
    Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, 115 Mill St, Belmont, MA 02478, USA
    Ann N Y Acad Sci 1129:256-60. 2008
    ..Moreover, we observed a significant association of the -3081(T) variant with ADHD. Altered transcription of SLC6A2 may therefore represent a novel risk factor for the development of ADHD...
  73. doi request reprint Aberrant trafficking of the high-affinity choline transporter in AP-3-deficient mice
    Hidemi Misawa
    Department of Pharmacology, Kyoritsu University of Pharmacy, Tokyo 105 8512, Japan
    Eur J Neurosci 27:3109-17. 2008
    ..The amounts of CHT detected on SLMV are greatly reduced by treating the cell with agents that halt AP-dependent membrane trafficking. These results demonstrate that APs have important functions for CHT trafficking in neuronal cells...
  74. ncbi request reprint Distribution of high affinity choline transporter immunoreactivity in the primate central nervous system
    Laura Kus
    Department of Neurological Sciences, Rush Presbyterian St Luke s Medical Center, Chicago, Illinois 60612
    J Comp Neurol 463:341-57. 2003
    ..The present observations indicate that the present CHT antibody labels cholinergic structures within the primate CNS and provides an additional marker for the investigation of cholinergic neuronal function in aging and disease...
  75. ncbi request reprint Serotonin and cocaine-sensitive inactivation of human serotonin transporters by methanethiosulfonates targeted to transmembrane domain I
    L Keith Henry
    Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232 8548, USA
    J Biol Chem 278:37052-63. 2003
    ..Moreover, we identify a limit to accessibility for membrane-impermeant MTS reagents that may reflect aspects of an occluded permeation pathway...
  76. ncbi request reprint Ultrastructural localization of the norepinephrine transporter in superficial and deep layers of the rat prelimbic prefrontal cortex and its spatial relationship to probable dopamine terminals
    LeeAnn H Miner
    Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Comp Neurol 466:478-94. 2003
    ..These results suggest that, in the rat PFC, NE axons (1) contain predominantly cytoplasmic NET, (2) infrequently contain TH immunolabeling, and (3) may interact with probable DA afferents by means of extrasynaptic mechanisms...
  77. ncbi request reprint Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells
    Becky J Proskocil
    Division of Neuroscience, Oregon National Primate Research Center, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA
    Endocrinology 145:2498-506. 2004
    ..This pathway may also explain some of the effects of nicotine on fetal development and also provides additional mechanisms by which smoking affects lung cancer growth and development...
  78. ncbi request reprint Ultrastructural interactions between terminals expressing the norepinephrine transporter and dopamine neurons in the rat and monkey ventral tegmental area
    Lindsay A Liprando
    Departments of Neuroscience and Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Synapse 52:233-44. 2004
    ..The latter finding agrees with observations in cortical regions and represents the first report of its type in a subcortical structure...
  79. ncbi request reprint Regulation of choline transporter surface expression and phosphorylation by protein kinase C and protein phosphatase 1/2A
    Jeremiah Gates
    Department of Anatomy and Neurobiology, University of Kentucky Medical Center, 306 Whitney Hendrickson Building, 800 Rose Street, Lexington, KY 40536 0098, USA
    J Pharmacol Exp Ther 310:536-45. 2004
    ..These studies also provide the first evidence that CHT is a phosphoprotein and that the basal PP1/PP2A activity may have a dominant role in controlling the levels of CHT phosphorylation...

Research Grants32

  1. Genes Controlling Assembly and Function of Serotonin Systems
    Randy Blakely; Fiscal Year: 2007
    ....
  2. REGULATION OF SEROTONIN TRANSPORTERS
    Randy D Blakely; Fiscal Year: 2010
    ....
  3. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2001
    ....
  4. ACUTE REGULATION OF NOREPINEPHRINE TRANSPORTERS
    Randy Blakely; Fiscal Year: 2000
    ..Data from these studies should substantially augment our understanding of presynaptic control mechanisms involved in sympathetic neurotransmission. ..
  5. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 1999
    ....
  6. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2007
    ..abstract_text> ..
  7. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2009
    ....
  8. Transgenic Mouse Model to Address Heterogeneity in Autism Spectrum Disorders
    Randy Blakely; Fiscal Year: 2009
    ..Based on exciting preliminary evidence that mice expressing Ala56 SERT exhibit multiple behavioral and biochemical phenotypes, we propose a two-year project to extend our studies and dissect the impact of SERT hyperfunction in vivo. ..
  9. Transgenic Mouse Model to Address Heterogeneity in Autism Spectrum Disorders
    RANDY DEAN BLAKELY; Fiscal Year: 2010
    ..Based on exciting preliminary evidence that mice expressing Ala56 SERT exhibit multiple behavioral and biochemical phenotypes, we propose a two-year project to extend our studies and dissect the impact of SERT hyperfunction in vivo. ..
  10. Molecular Analysis of Presynaptic Choline Transporters
    Randy Blakely; Fiscal Year: 2007
    ..These studies will elucidate novel aspects of CHT regulation, clarify how CHT supports cholinergic synaptic/behavioral plasticity and provide new CHT links to brain disease. ..
  11. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2007
    ....
  12. Postdoctoral Training Program in Neurogenomics
    Randy Blakely; Fiscal Year: 2006
    ..Our program provides for formal research training and didactic instruction, as well as seminars and technical workshops at the interface of neuroscience and genomic research. ..
  13. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2000
    ....
  14. ACUTE REGULATION OF NOREPINEPHRINE TRANSPORTERS
    Randy Blakely; Fiscal Year: 1999
    ..Data from these studies should substantially augment our understanding of presynaptic control mechanisms involved in sympathetic neurotransmission. ..
  15. ACUTE REGULATION OF NOREPINEPHRINE TRANSPORTERS
    Randy Blakely; Fiscal Year: 2000
    ..Data from these studies should substantially augment our understanding of presynaptic control mechanisms involved in sympathetic neurotransmission. ..
  16. ACUTE REGULATION OF NOREPINEPHRINE TRANSPORTERS
    Randy Blakely; Fiscal Year: 2001
    ..Data from these studies should substantially augment our understanding of presynaptic control mechanisms involved in sympathetic neurotransmission. ..
  17. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2002
    ....
  18. A Neurogenomic Model for Dopamine Transporter Regulation
    Randy Blakely; Fiscal Year: 2002
    ..elegans DAT (CeDAT) expression in cultured DA neurons and 2) to develop a system where a combination of transgenic and proteomic approaches can be applied to permit the evaluation of hypothesized and novel DAT regulators. ..
  19. ACUTE REGULATION OF NOREPINEPHRINE TRANSPORTERS
    Randy Blakely; Fiscal Year: 2002
    ..Data from these studies should substantially augment our understanding of presynaptic control mechanisms involved in sympathetic neurotransmission. ..
  20. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2003
    ....
  21. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2006
    ....
  22. REGULATION OF SEROTONIN TRANSPORTERS
    Randy Blakely; Fiscal Year: 2005
    ....