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Lynx1 Shifts α4β2 Nicotinic Receptor Subunit Stoichiometry by Affecting Assembly in the Endoplasmic Reticulum

Nichols, Weston A. and Henderson, Brandon J. and Yu, Caroline and Parker, Rell L. and Richards, Christopher I. and Lester, Henry A. and Miwa, Julie M. (2014) Lynx1 Shifts α4β2 Nicotinic Receptor Subunit Stoichiometry by Affecting Assembly in the Endoplasmic Reticulum. Journal of Biological Chemistry, 289 (45). pp. 31423-31432. ISSN 0021-9258. PMCID PMC4223341. doi:10.1074/jbc.M114.573667. https://resolver.caltech.edu/CaltechAUTHORS:20140915-092705574

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Abstract

GPI-anchored neurotoxin-like receptor binding proteins, such as lynx modulators, are topologically positioned to exert pharmacological effects by binding to the extracellular portion of nAChRs. These actions are generally thought to proceed when both lynx and the nAChRs are on the plasma membrane. Here, we demonstrate that lynx1 also exerts effects on α4β2 nAChRs within the endoplasmic reticulum. Lynx1 affects assembly of nascent α4 and β2 subunits, and alters the stoichiometry of the population that reaches the plasma membrane. Additionally, these data suggest that lynx1 shifts nAChR stoichiometry to low sensitivity (α4)_3 (β2)_2 pentamers primarily through this interaction in the endoplasmic reticulum, rather than solely via direct modulation of activity on the plasma membrane To our knowledge, these data represent the first test of the hypothesis that a lynx family member, or indeed any GPI-anchored protein, could act within the cell to alter assembly of multi-subunit protein.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1074/jbc.M114.573667DOIArticle
http://www.jbc.org/content/289/45/31423.longPublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223341/PubMed CentralArticle
ORCID:
AuthorORCID
Henderson, Brandon J.0000-0003-0381-028X
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2014 The American Society for Biochemistry and Molecular Biology. Received April 23, 2014; accepted September 5, 2014. Thanks to Sheri McKinney for providing hippocampal neuron cultures. We also thank R. Srinivasan and M. Starbird for comments and technical advice. This research was supported by TRDRP 19KT-0032 and by the National Institutes of Health (DA033831, NS034407, EY018502, MH088550).
Funders:
Funding AgencyGrant Number
California Tobacco-Related Disease Research Program19KT-0032
NIHDA033831
NIHNS034407
NIHEY018502
NIHMH088550
Subject Keywords:Cys-loop receptor; glycosylphosphatidylinositol (GPI anchor); nicotinic acetylcholine receptors (nAChR); snake venom; toxin
Issue or Number:45
PubMed Central ID:PMC4223341
DOI:10.1074/jbc.M114.573667
Record Number:CaltechAUTHORS:20140915-092705574
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20140915-092705574
Official Citation:Weston A. Nichols, Brandon J. Henderson, Caroline Yu, Rell L. Parker, Christopher I. Richards, Henry A. Lester, and Julie M. Miwa Lynx1 Shifts α4β2 Nicotinic Receptor Subunit Stoichiometry by Affecting Assembly in the Endoplasmic Reticulum J. Biol. Chem. 2014 289: 31423-. doi:10.1074/jbc.M114.573667
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:49689
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:15 Sep 2014 18:16
Last Modified:10 Nov 2021 18:47

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