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    
Abstract/OtherAbstract:
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.
Authors:
Qian Li; Yuan-Yuan Su; Hao Wang; Lei Li; Qiong Wang; Lan Bao
Related Documents :
16678949 - Biodegradation studies of selected priority acidic pesticides and diclofenac in differe...
23949659 - The association between n-3 polyunsaturated fatty acid levels in erythrocytes and the r...
1495979 - The two-step conversion of big endothelin 1 to endothelin 1 and degradation of endothel...
15032869 - Sequence of morphological and physiological events during natural ageing and senescence...
811029 - Studies on the degradation of pterine and pterine-6-carboxylic acid by pseudomonas fluo...
15248459 - Stability control of valerian ground material and extracts: a new hplc-method for the r...
22360639 - Cycloartane and friedelane triterpenoids from the leaves of caloncoba glauca and their ...
19913689 - Evaluation of the efficacy of four weak acids as antifungal preservatives in low-acid i...
16478959 - Ruminal in situ disappearance kinetics of nitrogen and neutral detergent insoluble nitr...
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    
Affiliation:
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Animals
COS Cells
Calnexin / genetics,  metabolism*
Cell Membrane / genetics,  metabolism*
Cercopithecus aethiops
Endoplasmic Reticulum / genetics,  metabolism*
Gene Expression Regulation / physiology*
Humans
Male
NAV1.8 Voltage-Gated Sodium Channel
Protein Structure, Tertiary
Rats
Rats, Sprague-Dawley
Sodium Channels / biosynthesis*,  genetics
Chemical
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
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Time of day and nutrients in feeding govern daily expression rhythms of the gene for sterol regulato...
Next Document:  ATBF1 inhibits estrogen receptor (ER) function by selectively competing with AIB1 for binding to the...