Research Topics
| Richard MainsSummaryAffiliation: University of Connecticut Health Center Country: USA Publications
Research Grants
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Detail Information
Publications
Kalrn plays key roles within and outside of the nervous systemPrashant Mandela
Department of Neuroscience, University of Connecticut Health Science Center, Farmington, CT, 06030 3401, USA
BMC Neurosci 13:136. 2012..abstract:..- Analysis of kalirin-7 knockout mice reveals different effects in female miceChristopher M Mazzone
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030 3401, USA
Mol Pharmacol 82:1241-9. 2012..The differing behavioral effects of Kal7 ablation in female and male mice may offer insight into the molecular underpinnings of these differences... - Kalirin12 interacts with dynaminXiaonan Xin
Neuroscience Department, University of Connecticut Health Center, Farmington, USA
BMC Neurosci 10:61. 2009..Dynamin, a large force-generating GTPase, plays an essential role in membrane tubulation and fission in cells. Kalirin12, a neuronal RhoGEF, is found in growth cones early in development and in dendritic spines later in development... - Dynamics of peptidergic secretory granule transport are regulated by neuronal stimulationJacqueline A Sobota
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030 3401, USA
BMC Neurosci 11:32. 2010..Since peptide granules cannot be refilled locally after their contents are secreted, it is particularly important to understand how neurons support regulated release of peptides... - Kalrn promoter usage and isoform expression respond to chronic cocaine exposureRichard E Mains
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030 3401, USA
BMC Neurosci 12:20. 2011.... - Kalirin-7 is required for synaptic structure and functionXin Ming Ma
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
J Neurosci 28:12368-82. 2008..Expression of exogenous Kal7 in Kal7(KO) neurons rescued this deficit. Kal7 plays an essential role in synaptic structure and function, affecting a subset of cognitive processes... 
Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirinPeter Penzes
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Neuron 37:263-74. 2003..This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity...- Kalirin, a multifunctional Rho guanine nucleotide exchange factor, is necessary for maintenance of hippocampal pyramidal neuron dendrites and dendritic spinesXin Ming Ma
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030 3401, USA
J Neurosci 23:10593-603. 2003..Pyramidal cell axons were not dramatically altered. Although many factors determine dendrite shape and spine formation, expression of Kalirin is necessary for the normal function of these many regulatory elements... - Kalirin/Trio Rho guanine nucleotide exchange factors regulate a novel step in secretory granule maturationFrancesco Ferraro
Neuroscience Department, University of Connecticut Health Center, Farmington, CT 06030 3401, USA
Mol Biol Cell 18:4813-25. 2007..Control of this step enhances the range of physiological responses that can be elicited, whereas lack of control could have pathological consequences... - Autonomous functions for the Sec14p/spectrin-repeat region of KalirinMartin R Schiller
Department of Molecular, Microbial, and Structural Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Exp Cell Res 314:2674-91. 2008..We conclude that the Sec14p and N-terminal spectrin-like domains of Kalirin play critical roles in distinguishing the actions of full-length and Delta-Kalirin proteins... - Kalirin-7 is an essential component of both shaft and spine excitatory synapses in hippocampal interneuronsXin Ming Ma
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
J Neurosci 28:711-24. 2008..Kal7 thus joins Shank3 and GluR2 as molecules with a level of expression at excitatory synapses that titrates the number of dendritic spines... - Induction of lamellipodia by Kalirin does not require its guanine nucleotide exchange factor activityMartin R Schiller
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030 3401, USA
Exp Cell Res 307:402-17. 2005..Together, our results indicate that Kal-GEF1 induces lamellipodia through activation of Pak, where GEF activity is not required. GEF-activity-independent effects on downstream targets may be a general property of RhoGEFs... - Expression of Trio, a member of the Dbl family of Rho GEFs in the developing rat brainXin Ming Ma
University of Connecticut Health Center, Department of Neuroscience, MC 3401, 263 Farmington Ave, Farmington, Connecticut 06030, USA
J Comp Neurol 482:333-48. 2005..The data suggest that Trio plays an important role during neuronal development... - Genomic organization and differential expression of Kalirin isoformsClifton E McPherson
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030 3401, USA
Gene 284:41-51. 2002..The prevalence of Kalirin in the cortex throughout life suggests roles in axonal development and the mature brain... - Multiple novel isoforms of Trio are expressed in the developing rat brainClifton E McPherson
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030 3401, USA
Gene 347:125-35. 2005..Trio/duet is expressed in adult cortex and cerebellum. In the rat brain, each of these Trio isoforms is expressed at a higher level than full length Trio... - Kalirin expression is regulated by multiple promotersClifton E McPherson
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA
J Mol Neurosci 22:51-62. 2004..Most of these alternate first exons lie >100 kb upstream of exon 2 in both rats and humans. Comparisons of the rat and human Kalirin promoter regions reveal numerous shared potential regulatory elements... - Routing of membrane proteins to large dense core vesicles in PC12 cellsRuth Marx
Department of Neuroscience, University of Connecticut Health Center, Farmington 06030-3401, USA
J Mol Neurosci 18:113-27. 2002..Thus, the lumenal PAM catalytic domains are not required for routing or phosphorylation of PAM in PC12 cells... - Cdk5 and Trio modulate endocrine cell exocytosisXiaonan Xin
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
J Cell Sci 117:4739-48. 2004..Together, these data suggest that control of the cortical actin cytoskeleton, long known to modulate hormone exocytosis and subsequent endocytosis, involves Cdk5-mediated activation of Trio... - Regulation of Kalirin by Cdk5Xiaonan Xin
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030 3401, USA
J Cell Sci 121:2601-11. 2008..The presence of Thr1590 in each major Kalirin isoform would allow Cdk5 to regulate Kalirin function throughout development... - Kalirin: a dual Rho guanine nucleotide exchange factor that is so much more than the sum of its many partsChana A Rabiner
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Neuroscientist 11:148-60. 2005..These interactions have implications not only for neuronal morphogenesis but also for vesicle trafficking, secretion, neuronal maintenance, and neurodegenerative disease... - Trafficking of a secretory granule membrane protein is sensitive to copperMithu De
University of Connecticut Health Center, Farmington, Connecticut 06030 3401, USA
J Biol Chem 282:23362-71. 2007..The response of PAM to lack of copper suggests that it facilitates copper homeostasis... - ATP7A (Menkes protein) functions in axonal targeting and synaptogenesisRajaa El Meskini
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA
Mol Cell Neurosci 34:409-21. 2007..This study demonstrates a role for ATP7A and/or copper in axon outgrowth and synaptogenesis, and will further help identify the cause of the neuropathology that characterizes MD... - Plasticity in hippocampal peptidergic systems induced by repeated electroconvulsive shockXin Ming Ma
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Neuropsychopharmacology 27:55-71. 2002..The distinctly different effects of repeated vs. acute electroconvulsive shock support an important role for peptidergic plasticity in the therapeutic effects observed following electroconvulsive treatment... - Not all secretory granules are created equal: Partitioning of soluble content proteinsJacqueline A Sobota
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030 3401, USA
Mol Biol Cell 17:5038-52. 2006.... - Signaling from the secretory granule to the nucleus: Uhmk1 and PAMVictor P Francone
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06032, USA
Mol Endocrinol 24:1543-58. 2010..Expression of PAM-CD also increased Aqp1 levels whereas expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent... - Behavioral and morphological responses to cocaine require kalirin7Drew D Kiraly
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, USA
Biol Psychiatry 68:249-55. 2010..Despite numerous reports of these findings, the molecular mechanisms leading to these morphological, biochemical, and behavioral changes remain unclear... - Secretory granule to the nucleus: role of a multiply phosphorylated intrinsically unstructured domainChitra Rajagopal
Department of Molecular, Microbial, and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
J Biol Chem 284:25723-34. 2009..This multiply phosphorylated unstructured domain may act as a signaling molecule that relays information from secretory granules to both cytosol and nucleus... - Retrieval and reuse of pituitary secretory granule proteinsFrancesco Ferraro
Neuroscience Department, University of Connecticut Health Center, Farmington, Connecticut 06030 3401, USA
J Biol Chem 280:25424-35. 2005..Thus, pituitary cells can retrieve and reuse components of the machinery involved in the final stages of exocytosis (the SNAREs) as well as soluble and membrane granule proteins... - Secretion stimulates intramembrane proteolysis of a secretory granule membrane enzymeChitra Rajagopal
Departments of Molecular, Microbial, and Structural Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA
J Biol Chem 285:34632-42. 2010..sf-CD is produced by primary rat anterior pituitary cells in response to secretogogue, suggesting that sf-CD acts as a signaling molecule relaying information about secretion from the secretory granule to the nucleus... - Enzymatic activity of soluble and membrane tethered peptide pro-hormone convertase 1Angela Bruzzaniti
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Peptides 23:863-75. 2002..Both tethers allow PC1 to visit the cell surface transiently, cleaving soluble molecules outside the cell. Both membrane-bound PC1 chimeras cleave membrane PAM into soluble active fragments when PAM is expressed on adjacent cells... - Role for an essential tyrosine in peptide amidationMithu De
Neuroscience Department, University of Connecticut Health Center, Farmington, 06030-3401, USA
J Biol Chem 281:20873-82. 2006..Our data demonstrate an essential role for Tyr(654) and suggest that it serves as an Fe(III) ligand in an essential iron-zinc bimetallic site... - Menkes protein contributes to the function of peptidylglycine alpha-amidating monooxygenaseTami C Steveson
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030 3401, USA
Endocrinology 144:188-200. 2003..Based on these results, we conclude that a reduction in the ability of PAM to produce bioactive end-products involved in neuronal growth and development could contribute to many of the biological effects associated with Menkes disease... - Monooxygenase X, a member of the copper-dependent monooxygenase family localized to the endoplasmic reticulumXiaonan Xin
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030 3401, USA
J Biol Chem 279:48159-67. 2004..MOX is N-glycosylated, is tightly membrane-associated, and forms oligomers that are not disulfide-linked. Based on its sequence and localization, MOX is predicted to hydroxylate a hydrophobic substrate in the endoplasmic reticulum... - Altered ATP7A expression and other compensatory responses in a murine model of Menkes diseaseMark J Niciu
University of Connecticut Health Center, Department of Neuroscience, Academic Research Building E 4047 1, 263 Farmington Avenue, Farmington, CT 06030 3401, USA
Neurobiol Dis 27:278-91. 2007..The compensatory changes observed in the neurovascular unit provide insight into the success of copper injections within a defined neurodevelopmental period... - Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanismsVictor May
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, Vermont 05404, USA
J Neurosci 22:6980-90. 2002..Thus Kalirin, acting via RhoG in a novel manner, plays a central role in establishing the morphological phenotypic diversity that is essential to the connectivity of the developing nervous system... - Fluoride causes reversible dispersal of Golgi cisternae and matrix in neuroendocrine cellsNils Bäck
Department of Anatomy, Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Finland
Eur J Cell Biol 83:389-402. 2004..Instead of a specific aluminum fluoride effect on secretory granule formation in the trans-Golgi network, we thus observe a unique form of Golgi dispersal induced by fluoride alone, possibly via its action as a phosphatase inhibitor... - The catalytic copper of peptidylglycine alpha-hydroxylating monooxygenase also plays a critical structural roleXavier Siebert
Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Biophys J 89:3312-9. 2005..Met(314)Ile-PHM was also shown to be less stable than wt-PHM by differential scanning calorimetry. Both structural and calorimetric studies point to a structural role for the CuM site, in addition to its established catalytic role... - Drosophila uses two distinct neuropeptide amidating enzymes, dPAL1 and dPAL2Mei Han
Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, Missouri, USA
J Neurochem 90:129-41. 2004..dPAL1 expression is highly correlated with the non-amidated peptide proctolin. Tissue immunostaining demonstrates that dPAL1 is largely localized to the cell soma, whereas dPAL2 is distributed throughout neuronal processes...
Research Grants
- Dissecting the role of one neuronal RhoGEF amongst many: the Kalirin-7 null mouseRichard E Mains; Fiscal Year: 2010..We plan to use the Kalirin-7 knockout mouse that we generated to elucidate the pathway(s) controlling spine formation and structure. ..
- CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETIONRichard E Mains; Fiscal Year: 2010....
- CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETIONRichard Mains; Fiscal Year: 2007..With a mechanistic understanding of some of the ways in which secretory granules communicate to the surrounding cytosol, therapeutic means of controlling hormone secretion can be sought. ..
- Constructing a Conditional Kalirin Null MouseRichard Mains; Fiscal Year: 2005..Both will be bred with available tissue-specific and drug-inducible Cre recombinase mice. Aim 2 will examine the biochemical, histological, and developmental consequences of tissue-specific Kalirin conditional knockouts. ..
- CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETIONRichard Mains; Fiscal Year: 2002..Binding interactions of the pleckstrin homology and src homology 3 domains of Kalirin will be identified. ..
- CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETIONRichard E Mains; Fiscal Year: 2010....