Document Detail


Receptor-transporting protein 1 short (RTP1S) mediates translocation and activation of odorant receptors by acting through multiple steps.
MedLine Citation:
PMID:  22570474     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Odorant receptor (OR) proteins are retained in the endoplasmic reticulum when heterologously expressed in cultured cells of non-olfactory origins. RTP1S is an accessory protein to mammalian ORs and facilitates their trafficking to the cell-surface membrane and ligand-induced responses in heterologous cells. The mechanism by which RTP1S promotes the functional expression of ORs remains poorly understood. To obtain a better understanding of the role(s) of RTP1S, we performed a series of structure-function analyses of RTP1S in HEK293T cells. By constructing RTP1S deletion and chimera series and subsequently introducing single-site mutations into the protein, we found the N terminus of RTP1S is important for the endoplasmic reticulum exit of ORs and that a middle region of RTP1S is important for OR trafficking from the Golgi to the membrane. Using sucrose gradient centrifugation, we found that the localization of RTP1S to the lipid raft microdomain is critical to the activation of ORs. Finally, in a protein-protein interaction analysis, we determined that the C terminus of RTP1S may be interacting with ORs. These findings provide new insights into the distinct roles of RTP1S in OR translocation and activation.
Authors:
Lifang Wu; Yi Pan; Guo-Qiang Chen; Hiroaki Matsunami; Hanyi Zhuang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-08
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-25     Completed Date:  2012-09-20     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22287-94     Citation Subset:  IM    
Affiliation:
Department of Pathophysiology, Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
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MeSH Terms
Descriptor/Qualifier:
Flow Cytometry / methods
HEK293 Cells
Humans
Immunohistochemistry / methods
Ligands
Membrane Microdomains / metabolism
Membrane Transport Proteins / chemistry*,  physiology
Models, Biological
Plasmids / metabolism
Protein Structure, Tertiary
Protein Transport
Receptors, G-Protein-Coupled / metabolism
Receptors, Odorant / metabolism*
Grant Support
ID/Acronym/Agency:
DC005782/DC/NIDCD NIH HHS; R01 DC010857/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Ligands; 0/Membrane Transport Proteins; 0/RTP1 protein, human; 0/Receptors, G-Protein-Coupled; 0/Receptors, Odorant
Comments/Corrections

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