| GRIN1 regulates micro-opioid receptor activities by tethering the receptor and G protein in the lipid raft. | |
| | |
MedLine Citation:
|
PMID: 19861419 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The lipid raft location of mu-opioid receptor (MOR) determines the receptor activities. However, the manner in which MOR is anchored within the lipid rafts is undetermined. Using the targeted proteomic approach and mass spectrometry analyses, we have identified GRIN1 (G protein-regulated inducer of neurite outgrowth 1) can tether MOR with the G protein alpha-subunit and subsequently regulate the receptor distribution within the lipid rafts. Glutathione S-transferase fusion pulldown and receptor mutational analyses indicate that GRIN1-MOR interaction involves a receptor sequence (267)GSKEK(271) within the MOR third intracellular loop that is not involved in Galpha interaction. The GRIN1 domains involved in MOR interaction are also distinct from those involved in Galpha interaction. Pertussis toxin pretreatment reduced the amount of GRIN1 co-immunoprecipitated with MOR but not the amount with Galpha. Furthermore, overexpression of GRIN1 significantly enhanced the amount of MOR in lipid raft and the receptor signaling magnitude as measured by Src kinase activation. Such increase in MOR signaling was demonstrated further by determining the GRIN1-dependent pertussis toxin-sensitive neurite outgrowth. In contrast to minimal neurite outgrowth induced by etorphine in control neuroblastoma N2A cells, overexpression of GRIN1 resulted in the increase in etorphine- and non-morphine-induced neurite outgrowth in these cells. Knocking down endogenous GRIN1 by small interfering RNA attenuated the agonist-induced neurite outgrowth. Disrupting lipid raft by methyl-beta-cyclodextrin also blocked neurite outgrowth. Hence, by tethering Galpha with MOR, GRIN1 stabilizes the receptor within the lipid rafts and potentiates the receptor signaling in the neurite outgrowth processes. |
| | |
Authors:
|
Xin Ge; Yu Qiu; Horace H Loh; Ping-Yee Law |
Related Documents
:
|
15485769 - Retrograde propagation of gdnf-mediated signals in sympathetic neurons. 18634579 - Two distinct mechanisms segregate prospero in the longitudinal glia underlying the timi... 15145949 - Epha receptors direct the differentiation of mammalian neural precursor cells through a... 16020529 - Ephrin-b3 is a myelin-based inhibitor of neurite outgrowth. 11972959 - Ephrins are not only unattractive. 10383829 - A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates ne... 11734569 - Scavenger receptor class b type i affects cholesterol homeostasis by magnifying cholest... 2054829 - Effects of acetylcholine on different muscarinic receptors in the perfused porcine ear ... 9435519 - [pro11,d-ala12]angiotensin i has rapid onset vasoconstrictor activity in the cat. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-10-27 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 284 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Dec |
Date Detail:
|
Created Date: 2009-12-21 Completed Date: 2010-01-08 Revised Date: 2010-12-28 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 36521-34 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. gexx0019@umn.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Analgesics, Opioid
/
pharmacology Animals Cell Line, Tumor Etorphine / pharmacology GTP-Binding Protein alpha Subunits / genetics, metabolism* Gene Knockdown Techniques Male Membrane Microdomains / genetics, metabolism* Neurites / metabolism* Protein Structure, Secondary / genetics Protein Structure, Tertiary / genetics RNA, Small Interfering Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate / genetics, metabolism* Receptors, Opioid, mu / genetics, metabolism* Signal Transduction / drug effects, genetics beta-Cyclodextrins / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
|
DA000564/DA/NIDA NIH HHS; DA007339/DA/NIDA NIH HHS; DA011806/DA/NIDA NIH HHS; DA016674/DA/NIDA NIH HHS; K05-DA00513/DA/NIDA NIH HHS; K05-DA70544/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Analgesics, Opioid; 0/GTP-Binding Protein alpha Subunits; 0/NMDA receptor A1; 0/RNA, Small Interfering; 0/Receptors, N-Methyl-D-Aspartate; 0/Receptors, Opioid, mu; 0/beta-Cyclodextrins; 0/methyl-beta-cyclodextrin; 14521-96-1/Etorphine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Calcium-activated calpain-2 is a mediator of beta cell dysfunction and apoptosis in type 2 diabetes.
Next Document: Structural features of the tmRNA-ribosome interaction.