This is an application for a renewal of a NIDA sponsored K02 Independent Scientist Award. G protein-coupled receptors (GPCRs) comprise the largest known family of signaling receptors, mediate diverse functions in the CNS, are critical targets for drugs of abuse, and are extensively regulated in vivo. One mechanism of receptor regulation, on which clinically relevant drugs can have diverse effects, involves regulated membrane trafficking of receptors through the endocytic pathway. In previous studies a specific mechanism by which opioid neuropeptide receptors undergo initial endocytosis from the plasma membrane was identified and investigated. The current proposal seeks to elucidate mechanisms by which the endocytic membrane trafficking of G protein-coupled opioid receptors is controlled after endocytosis.
The Specific Aims of the proposed studies are to: (1) Define the biochemical properties of a mechanism that mediates signal-dependent recycling of opioid receptors; (2) Elucidate a distinct mechanism that promotes sorting of endocvtosed opioid receptors to lysosomes; (3) Determine whether opioid receptors are sorted between distinct membrane domains of multivesicular endosomes; and (4) Investigate the functional relevance of specific post-endocytic sorting mechanisms to opioid receptor regulation in neurons. These studies have general relevance to understanding mechanisms by which G protein-coupled receptors are regulated, and will contribute fundamental information to understanding physiological adaptation of the nervous system in response to clinically important opiate drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA000439-09
Application #
7462339
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Koustova, Elena
Project Start
1999-09-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
9
Fiscal Year
2008
Total Cost
$118,584
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Ikemoto, Satoshi; Qin, Mei; Liu, Zhong-Hua (2006) Primary reinforcing effects of nicotine are triggered from multiple regions both inside and outside the ventral tegmental area. J Neurosci 26:723-30

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