Document Detail

Transmembrane segments prevent surface expression of sodium channel Nav1.8 and promote calnexin-dependent channel degradation.
MedLine Citation:
PMID:  20720009     Owner:  NLM     Status:  MEDLINE    
The voltage-gated sodium channel (Na(v)) 1.8 contributes substantially to the rising phase of action potential in small dorsal root ganglion neurons. Na(v)1.8 is majorly localized intracellularly and its expression on the plasma membrane is regulated by exit from the endoplasmic reticulum (ER). Previous work has identified an ER-retention/retrieval motif in the first intracellular loop of Na(v)1.8, which prevents its surface expression. Here we report that the transmembrane segments of Na(v)1.8 also cause this channel retained in the ER. Using transferrin receptor and CD8α as model molecules, immunocytochemistry showed that the first, second, and third transmembrane segments in each domain of Na(v)1.8 reduced their surface expression. Alanine-scanning analysis revealed acidic amino acids as critical factors in the odd transmembrane segments. Furthermore, co-immunoprecipitation experiments showed that calnexin interacted with acidic amino acid-containing sequences through its transmembrane segment. Overexpression of calnexin resulted in increased degradation of those proteins through the ER-associated degradation pathway, whereas down-regulation of calnexin reversed the phenotype. Thus our results reveal a critical role and mechanism of transmembrane segments in surface expression and degradation of Na(v)1.8.
Qian Li; Yuan-Yuan Su; Hao Wang; Lei Li; Qiong Wang; Lan Bao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-18
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2010-11-24     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32977-87     Citation Subset:  IM    
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
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MeSH Terms
Amino Acid Motifs
COS Cells
Calnexin / genetics,  metabolism*
Cell Membrane / genetics,  metabolism*
Cercopithecus aethiops
Endoplasmic Reticulum / genetics,  metabolism*
Gene Expression Regulation / physiology*
NAV1.8 Voltage-Gated Sodium Channel
Protein Structure, Tertiary
Rats, Sprague-Dawley
Sodium Channels / biosynthesis*,  genetics
Reg. No./Substance:
0/NAV1.8 Voltage-Gated Sodium Channel; 0/SCN10A protein, human; 0/Scn10a protein, rat; 0/Sodium Channels; 139873-08-8/Calnexin

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