Jennifer Whistler

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint A phosphorylation-regulated brake mechanism controls the initial endocytosis of opioid receptors but is not required for post-endocytic sorting to lysosomes
    J L Whistler
    Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA
    J Biol Chem 276:34331-8. 2001
  2. ncbi request reprint Constitutive activation and endocytosis of the complement factor 5a receptor: evidence for multiple activated conformations of a G protein-coupled receptor
    Jennifer L Whistler
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, California, USA
    Traffic 3:866-77. 2002
  3. ncbi request reprint Modulation of postendocytic sorting of G protein-coupled receptors
    Jennifer L Whistler
    Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA
    Science 297:615-20. 2002
  4. ncbi request reprint Changes in G protein-coupled receptor sorting protein affinity regulate postendocytic targeting of G protein-coupled receptors
    Dawn Thompson
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA
    J Biol Chem 282:29178-85. 2007
  5. pmc How to design an opioid drug that causes reduced tolerance and dependence
    Amy Chang Berger
    Department of Neurology, University of California, San Francisco, Ernest Gallo Clinic and Research Center, Emeryville, CA, USA
    Ann Neurol 67:559-69. 2010
  6. ncbi request reprint The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence
    Lene Martini
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton St Suite 200, Emeryville, CA 94608, United States
    Curr Opin Neurobiol 17:556-64. 2007
  7. ncbi request reprint The biochemical analysis of methadone modulation on morphine-induced tolerance and dependence in the rat brain
    Li He
    Ernest Gallo Clinic and Research Center and Department of Neurology, University of California at San Francisco, Emeryville, Calif 94608, USA
    Pharmacology 79:193-202. 2007
  8. ncbi request reprint An opiate cocktail that reduces morphine tolerance and dependence
    Li He
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA
    Curr Biol 15:1028-33. 2005
  9. pmc Functional characterization of human variants of the mu-opioid receptor gene
    Ajay Ravindranathan
    Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA
    Proc Natl Acad Sci U S A 106:10811-6. 2009
  10. ncbi request reprint Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization
    Li He
    Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608, USA
    Cell 108:271-82. 2002

Research Grants

Collaborators

Detail Information

Publications30

  1. ncbi request reprint A phosphorylation-regulated brake mechanism controls the initial endocytosis of opioid receptors but is not required for post-endocytic sorting to lysosomes
    J L Whistler
    Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA
    J Biol Chem 276:34331-8. 2001
    ..After endocytosis occurs, subsequent steps of membrane trafficking mediating sorting and transport to lysosomes do not require receptor phosphorylation...
  2. ncbi request reprint Constitutive activation and endocytosis of the complement factor 5a receptor: evidence for multiple activated conformations of a G protein-coupled receptor
    Jennifer L Whistler
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, California, USA
    Traffic 3:866-77. 2002
    ..Dissociation of two responses normally dependent on agonist binding indicates that the corresponding functions of an activated GPCR reflect different sets of changes in the receptor's conformation...
  3. ncbi request reprint Modulation of postendocytic sorting of G protein-coupled receptors
    Jennifer L Whistler
    Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA
    Science 297:615-20. 2002
    ..The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein-coupled receptors...
  4. ncbi request reprint Changes in G protein-coupled receptor sorting protein affinity regulate postendocytic targeting of G protein-coupled receptors
    Dawn Thompson
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA
    J Biol Chem 282:29178-85. 2007
    ..Together, these results indicate that alteration of receptors in their C termini can expose determinants with affinity for GASP binding and consequently target receptors for degradation...
  5. pmc How to design an opioid drug that causes reduced tolerance and dependence
    Amy Chang Berger
    Department of Neurology, University of California, San Francisco, Ernest Gallo Clinic and Research Center, Emeryville, CA, USA
    Ann Neurol 67:559-69. 2010
    ..We also discuss preliminary evidence that heteromers of the delta opioid receptor and the MOR are pronociceptive, and that drugs that spare such heteromers may also induce reduced tolerance...
  6. ncbi request reprint The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence
    Lene Martini
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton St Suite 200, Emeryville, CA 94608, United States
    Curr Opin Neurobiol 17:556-64. 2007
    ..As a consequence, facilitating receptor endocytosis, using either genetic or pharmacological approaches, can restore the balance of signaling through the receptor and affect the development of tolerance and dependence...
  7. ncbi request reprint The biochemical analysis of methadone modulation on morphine-induced tolerance and dependence in the rat brain
    Li He
    Ernest Gallo Clinic and Research Center and Department of Neurology, University of California at San Francisco, Emeryville, Calif 94608, USA
    Pharmacology 79:193-202. 2007
    ..Rather, brain-region-selective changes in adenylyl cyclase signal transduction are critical, and both these biochemical changes and the behavioral effects are prevented by facilitating endocytosis of the MOP receptor...
  8. ncbi request reprint An opiate cocktail that reduces morphine tolerance and dependence
    Li He
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA
    Curr Biol 15:1028-33. 2005
    ..We further demonstrate that dependence is reduced, at least in part, because endocytosis of the MOP receptor in response to morphine prevents the upregulation of N-methyl-D-aspartate (NMDA) receptors...
  9. pmc Functional characterization of human variants of the mu-opioid receptor gene
    Ajay Ravindranathan
    Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA
    Proc Natl Acad Sci U S A 106:10811-6. 2009
    ....
  10. ncbi request reprint Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization
    Li He
    Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608, USA
    Cell 108:271-82. 2002
    ..These results demonstrate that endocytosis of the MOR can reduce the development of tolerance, and hence suggest an approach for the development of opiate analogs with enhanced efficacy for the treatment of chronic pain...
  11. pmc Differential regulation of behavioral tolerance to WIN55,212-2 by GASP1
    Lene Martini
    Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA, USA
    Neuropsychopharmacology 35:1363-73. 2010
    ..Taken together, this study provides evidence that GASP1 regulates CB1 receptor downregulation in vivo, and that postendocytic receptor trafficking has a key role in the development of tolerance to WIN55,212-2...
  12. pmc Dopamine responsiveness is regulated by targeted sorting of D2 receptors
    Selena E Bartlett
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA 94608, USA
    Proc Natl Acad Sci U S A 102:11521-6. 2005
    ..Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors...
  13. pmc Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence
    Joseph A Kim
    Ernest Gallo Clinic and Research Center, 5858 Horton St, Suite 200, Emeryville, California 94608, USA
    Curr Biol 18:129-35. 2008
    ..These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence...
  14. ncbi request reprint Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G-protein-coupled receptor-associated sorting protein GASP1
    Lene Martini
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA, USA
    FASEB J 21:802-11. 2007
    ..Thus, these results may identify a molecular mechanism underlying tolerance and receptor down-regulation after long-term use of cannabinoids...
  15. pmc micro-Opioid receptor endocytosis prevents adaptations in ventral tegmental area GABA transmission induced during naloxone-precipitated morphine withdrawal
    Anuradha Madhavan
    Ernest Gallo Clinic and Research Center, Emeryville, California 94608, USA
    J Neurosci 30:3276-86. 2010
    ..5 microl), directly tying enhanced cAMP-driven GABA release to naloxone-precipitated morphine withdrawal in the VTA...
  16. pmc Opioid-receptor-heteromer-specific trafficking and pharmacology
    Richard M van Rijn
    Ernest Gallo Clinic and Research Center, University of California San Francisco, Department of Neurology, Emeryville, CA 94608, USA
    Curr Opin Pharmacol 10:73-9. 2010
    ..This review attempts to highlight some of the latest developments with regard to opioid receptor heteromer trafficking and pharmacology...
  17. pmc Biomarkers of morphine tolerance and dependence are prevented by morphine-induced endocytosis of a mutant mu-opioid receptor
    Li He
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, Emeryville, CA 94608, USA
    FASEB J 23:4327-34. 2009
    ..Together, these data demonstrate that morphine tolerance and dependence are mediated by multiple biochemical mechanisms and that MOR endocytosis plays a critical role in each of these mechanisms...
  18. pmc Opioid-Induced GABA potentiation after chronic morphine attenuates the rewarding effects of opioids in the ventral tegmental area
    Anuradha Madhavan
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA
    J Neurosci 30:14029-35. 2010
    ..Thus, a paradoxical bidirectionality in μ-receptor-mediated control of GABA transmission following chronic morphine treatment is a critical mechanism that determines the expression of opioid reward in the VTA...
  19. ncbi request reprint The near-death experience of delta opioid receptors leads to new drug targets
    Selena E Bartlett
    Ernest Gallo Clinic and Research Center, Emeryville CA 94608, USA
    Mol Interv 2:134-6. 2002
  20. pmc PKCepsilon regulates behavioral sensitivity, binding and tolerance to the CB1 receptor agonist WIN55,212-2
    Melisa J Wallace
    Department of Neurology, The Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608, USA
    Neuropsychopharmacology 34:1733-42. 2009
    ..These results indicate that PKCvarepsilon selectively regulates behavioral sensitivity, CB1 receptor binding and tolerance to WIN55,212-2...
  21. pmc Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine
    Dawn Thompson
    Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, California, USA
    PLoS ONE 5:e11038. 2010
    ....
  22. ncbi request reprint Opioid receptors
    Maria Waldhoer
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608, USA
    Annu Rev Biochem 73:953-90. 2004
    ..This review focuses on many aspects of opioid receptors with the aim of gaining a greater insight into mechanisms of opioid tolerance and dependence...
  23. pmc Methadone antinociception is dependent on peripheral opioid receptors
    Li He
    Ernest Gallo Clinic and Research Center and the Department of Neurology, University of California, San Francisco, Emeryville, CA 94608, USA
    J Pain 10:369-79. 2009
    ....
  24. pmc A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers
    Maria Waldhoer
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA 94608, USA
    Proc Natl Acad Sci U S A 102:9050-5. 2005
    ..Importantly, targeting opioid heterodimers could provide an approach toward the design of analgesic drugs with reduced side effects...
  25. pmc Dual efficacy of delta opioid receptor-selective ligands for ethanol drinking and anxiety
    Richard M van Rijn
    Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, Emeryville, CA 94608, USA
    J Pharmacol Exp Ther 335:133-9. 2010
    ..We believe the dual efficacy of DOR1 agonists makes these receptors an interesting therapeutic target for treatment-seeking alcoholics...
  26. pmc Acute amphetamine exposure selectively desensitizes kappa-opioid receptors in the nucleus accumbens
    Yan fang Xia
    Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA 94608, USA
    Neuropsychopharmacology 33:892-900. 2008
    ..This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure...
  27. ncbi request reprint A highly conserved glycine within linker I and the extreme C terminus of G protein alpha subunits interact cooperatively in switching G protein-coupled receptor-to-effector specificity
    Evi Kostenis
    7TM Pharma, Fremtidsvej 3, 2970 Hoersholm, Denmark
    J Pharmacol Exp Ther 313:78-87. 2005
    ....
  28. ncbi request reprint The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis
    Maria Waldhoer
    Laboratory for Molecular Pharmacology, Panum Institute, University of Copenhagen, Copenhagen DK 2200, Denmark
    J Biol Chem 278:19473-82. 2003
    ..This demonstrates for the first time that the endocytic properties of a 7TM receptor can camouflage the agonist properties of a ligand...
  29. ncbi request reprint mu-Opioid receptors: Ligand-dependent activation of potassium conductance, desensitization, and internalization
    Veronica A Alvarez
    Vollum Institute and Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, Oregon 97201, USA
    J Neurosci 22:5769-76. 2002
    ..Identification and characterization of the biophysical properties of agonists that favor desensitization and internalization of receptors will lead to a better understanding of opioid signaling...
  30. ncbi request reprint Kinins promote B2 receptor endocytosis and delay constitutive B1 receptor endocytosis
    Johan Enquist
    Department of Experimental Medical Science, Lund University, BMC, A12, S 22184 Lund, Sweden
    Mol Pharmacol 71:494-507. 2007
    ..These events provide a rapid kinin-dependent mechanism for 1) regulating the constitutive B1R activity and 2) shifting the balance of accessible receptors in favor of B1R...

Research Grants16

  1. Role of opioid receptor trafficking in tolerance and dependence
    Jennifer L Whistler; Fiscal Year: 2010
    ..Here we propose to utilize these mutant receptors to assess the molecular and behavioral effects of altered trafficking on the development of tolerance, withdrawal, and addiction. ..
  2. Role of opioid receptor trafficking in tolerance and dependence
    Jennifer Whistler; Fiscal Year: 2007
    ..Here we propose to utilize these mutant receptors to assess the molecular and behavioral effects of altered trafficking on the development of tolerance, withdrawal, and addiction. ..
  3. G Protein Coupled Receptor Trafficking and Opiate Drugs
    Jennifer Whistler; Fiscal Year: 2007
    ..abstract_text> ..
  4. GASP and Trafficking of the Dopamine Receptors
    Jennifer Whistler; Fiscal Year: 2007
    ..These studies will determine whether GPCR sorting can be manipulated both in vitro and in vivo. This may provide a new spectrum of therapeutic targets for the treatment of schizophrenia and depression. ..
  5. Trafficking and signaling of opioid receptor subtypes and heterodimers
    Jennifer L Whistler; Fiscal Year: 2010
    ..Thus targeting these subtypes or heterodimers could provide improved therapeutic utility. ..