Regulation of TRPV1 by a novel renally expressed rat TRPV1 splice variant

Wei Tian, Yi Fu, Donna H. Wang, David M. Cohen

Research output: Contribution to journalArticle

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Abstract

The capsaicin receptor and transient receptor potential channel TRPV1 senses heat, protons, and vanilloid agonists in peripheral sensory ganglia. Abundant data have suggested the presence of potentially novel splice variants in the kidney. We report a novel rat TRPV1 splice variant, TRPV1VAR, cloned from kidney papilla. TRPV1VAR cDNA was identified in multiple kidney tissues. Its sequence was fully compatible with potential splice donor and acceptor sites in the rat TRPV1 gene. TRPV1VAR is predicted to encode a truncated form of TRPV1 consisting of the NH2-terminal 248 residues of TRPV1 (all within the NH2-terminal intracellular domain) followed by five non-consensus amino acids (Arg-Glu-Ala-Met-Trp) and a stop codon. The variant utilizes the same consensus Kozak sequence as canonical TRPV1. A band of the appropriate molecular mass was identified in rat kidney papillary (but not medullary) lysates immunoblotted with an antibody directed against the NH2 terminus of TRPV1, whereas an antibody recognizing the TRPV1 COOH terminus failed to detect it. Upon heterologous expression in HEK 293 cells, TRPV1VAR potentiated the ability of cotransfected TRPV1 to confer calcium influx in response to resiniferatoxin. TRPV1VAR did not influence expression or cell surface localization of cotransfected TRPV1. TRPV1VAR protein product associated with the NH2 terminus of canonical TRPV1. Interestingly, when expressed in the COS-7 epithelial cell line, TRPV1VAR functioned in a dominant-negative acting capacity, partially blocking TRPV1-dependent resiniferatoxin responsiveness. We conclude that TRPV1VAR is one of perhaps several TRPV1 splice variants expressed in rat kidney and that it may serve to modulate TRPV1 responsiveness in some tissues.

Original languageEnglish (US)
Pages (from-to)F117-F126
JournalAmerican Journal of Physiology - Renal Physiology
Volume290
Issue number1
DOIs
StatePublished - Jan 1 2006

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Keywords

  • Transient receptor potential channel

ASJC Scopus subject areas

  • Physiology
  • Urology

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