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Whirlin increases TRPV1 channel expression and cellular stability
- Source :
- BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), Centro de Investigación Principe Felipe (CIPF), r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF), instname
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- The expression and function of TRPV1 are influenced by its interaction with cellular proteins. Here, we identify Whirlin, a cytoskeletal PDZ-scaffold protein implicated in hearing, vision and mechanosensory transduction, as an interacting partner of TRPV1. Whirlin associates with TRPV1 in cell lines and in primary cultures of rat nociceptors. Whirlin is expressed in 55% of mouse sensory C-fibers, including peptidergic and non-peptidergic nociceptors, and co-localizes with TRPV1 in 70% of them. Heterologous expression of Whirlin increased TRPV1 protein expression and trafficking to the plasma membrane, and promoted receptor clustering. Silencing Whirlin expression with siRNA or blocking protein translation resulted in a concomitant degradation of TRPV1 that could be prevented by inhibiting the proteasome. The degradation kinetics of TRPV1 upon arresting protein translation mirrored that of Whirlin in cells co-expressing both proteins, suggesting a parallel degradation mechanism. Noteworthy, Whirlin expression significantly reduced TRPV1 degradation induced by prolonged exposure to capsaicin. Thus, our findings indicate that Whirlin and TRPV1 are associated in a subset of nociceptors and that TRPV1 protein stability is increased through the interaction with the cytoskeletal scaffold protein. Our results suggest that the Whirlin-TRPV1 complex may represent a novel molecular target and its pharmacological disruption might be a therapeutic strategy for the treatment of peripheral TRPV1-mediated disorders. (C) 2015 Elsevier B.V. All rights reserved.
- Subjects :
- Nociception
0301 basic medicine
Scaffold protein
Proteasome Endopeptidase Complex
PDZ domain
TRPV Cation Channels
Pain
Biology
Cytoskeleton
PDZ
Synapsis
Thermosensory
Article
Mice
03 medical and health sciences
0302 clinical medicine
Animals
Gene silencing
RNA, Small Interfering
Rats, Wistar
Molecular Biology
Cells, Cultured
Regulation of gene expression
Protein Stability
musculoskeletal, neural, and ocular physiology
Membrane Proteins
Nociceptors
Cell Biology
Rats
Cell biology
030104 developmental biology
Gene Expression Regulation
nervous system
Membrane protein
Proteasome
Multiprotein Complexes
Proteolysis
lipids (amino acids, peptides, and proteins)
Receptor clustering
psychological phenomena and processes
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 01674889
- Volume :
- 1863
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Accession number :
- edsair.doi.dedup.....f7f536f793fe75301c5ee804a5b6695a