WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, October 7, 2009, 29(40):12625-12635; doi:10.1523/JNEUROSCI.1776-09.2009

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Wang, Y.
Right arrow Articles by Wang, Z.-Z.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, Y.
Right arrow Articles by Wang, Z.-Z.

 Previous Article  |  Next Article 

Cellular/Molecular
Mouse RIC-3, an Endoplasmic Reticulum Chaperone, Promotes Assembly of the {alpha}7 Acetylcholine Receptor through a Cytoplasmic Coiled-Coil Domain

Ying Wang,1,2 Yun Yao,2 Xiao-Qing Tang,2 and Zuo-Zhong Wang1,2,3 {dagger}

1Neuroscience Graduate Program, 2Zilkha Neurogenetic Institute, and 3Department of Cell and Neurobiology, University of Southern California Keck School of Medicine, Los Angeles, California 90033

Correspondence should be addressed to Dr. Ying Wang, University of Southern California, 1501 San Pablo Street, Room 423, Los Angeles, CA 90033. Email: yingw17{at}usc.edu

RIC-3 (resistant to inhibitor of cholinesterase) is a transmembrane protein, found in invertebrates and vertebrates, that modulates the surface expression of a variety of nicotinic acetylcholine receptors (nAChRs) in neurons and other cells. To understand its mechanism of action, we investigated the cellular location, transmembrane topology and cellular mechanism by which RIC-3 facilitates {alpha}7 assembly and surface expression in cultured mammalian cells. We show that the mouse protein is targeted to the ER by the first 31 aa which act as a cleavable signal sequence. The mature protein is a single-pass type I transmembrane protein whose N terminus resides in the lumen of the ER with the coiled-coil domain in the cytoplasm. RIC-3, which binds both unfolded and folded {alpha}7 subunits, facilitates the surface expression of receptor principally by promoting the folding and assembly of the {alpha}7 subunits in the ER into fully polymerized receptor. Functional analysis shows that facilitation of surface expression of {alpha}7 in mammalian cells is reduced in RIC-3 mutants lacking the signal peptide, the lumenal segment or the coiled-coil domain, but not in mutants lacking the long C-terminal region downstream of the coiled-coil domain. We show that the coiled-coil domain of mRIC-3 is not required for the interaction of mRIC-3 with {alpha}7, but does mediate a homotypic interaction between molecules of mRIC-3. We suggest that efficient assembly of the homomeric {alpha}7 nAChR may thus require mRIC-3 self-association through the cytoplasmic coiled-coil domain and suggest a model by which this may occur.

Received April 13, 2009; revised Aug. 27, 2009; accepted Sept. 2, 2009.

Correspondence should be addressed to Dr. Ying Wang, University of Southern California, 1501 San Pablo Street, Room 423, Los Angeles, CA 90033. Email: yingw17{at}usc.edu






 -
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-