ArticleThe Journal of biological chemistry2010
Transmembrane segments prevent surface expression of sodium channel Nav1.8 and promote calnexin-dependent channel degradation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.Journal of cell science · 2024Article
- Intramembrane client recognition potentiates the chaperone functions of calnexin.The EMBO journal · 2022Article
- Loss-of-function of Nav1.8/D1639N linked to human pain can be rescued by lidocaine.Pflugers Archiv : European journal of physiology · 2018Article
- A forward genetic screen identifies chaperone CNX-1 as a conserved biogenesis regulator ofThe Journal of general physiology · 2018Article
- A Chimeric NaV1.8 Channel Expression System Based on HEK293T Cell Line.Frontiers in pharmacology · 2018Article
- The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type CaScientific reports · 2017Article
- Molecular Chaperone Calnexin Regulates the Function ofFrontiers in molecular neuroscience · 2017Article
- Transmembrane domain quality control systems operate at the endoplasmic reticulum and Golgi apparatus.PloS one · 2017Article
- ERAD of proteins containing aberrant transmembrane domains requires ubiquitylation of cytoplasmic lysine residues.Journal of cell science · 2015Article
- Trafficking regulates the subcellular distribution of voltage-gated sodium channels in primary sensory neurons.Molecular pain · 2015Review
- GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells.The Biochemical journal · 2014Article
- Mutant ELOVL4 that causes autosomal dominant stargardt-3 macular dystrophy is misrouted to rod outer segment disks.Investigative ophthalmology & visual science · 2014Article
- KIF5B promotes the forward transport and axonal function of the voltage-gated sodium channel Nav1.8.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Conduits of life's spark: a perspective on ion channel research since the birth of neuron.Neuron · 2013Review
- Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu.Journal of virology · 2012Article
- Structural basis for the Trembler-J phenotype of Charcot-Marie-Tooth disease.Structure (London, England : 1993) · 2011Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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