Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex
Détails
ID Serval
serval:BIB_76BA873451BD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex
Périodique
EMBO Journal
ISSN
0261-4189 (Print)
Statut éditorial
Publié
Date de publication
04/2003
Volume
22
Numéro
7
Pages
1478-87
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr 1
Research Support, Non-U.S. Gov't --- Old month value: Apr 1
Résumé
TRPV5 and TRPV6 constitute the Ca(2+) influx pathway in a variety of epithelial cells. Here, we identified S100A10 as the first auxiliary protein of these epithelial Ca(2+) channels using yeast two-hybrid and GST pull-down assays. This S100 protein forms a heterotetrameric complex with annexin 2 and associates specifically with the conserved sequence VATTV located in the C-terminal tail of TRPV5 and TRPV6. Of these five amino acids, the first threonine plays a crucial role since the corresponding mutants (TRPV5 T599A and TRPV6 T600A) exhibited a diminished capacity to bind S100A10, were redistributed to a subplasma membrane area and did not display channel activity. Using GST pull-down and co-immunoprecipitation assays we demonstrated that annexin 2 is part of the TRPV5-S100A10 complex. Furthermore, the S100A10-annexin 2 pair colocalizes with the Ca(2+) channels in TRPV5-expressing renal tubules and TRPV6-expressing duodenal cells. Importantly, downregulation of annexin 2 using annexin 2-specific small interfering RNA inhibited TRPV5 and TRPV6-mediated currents in transfected HEK293 cells. In conclusion, the S100A10-annexin 2 complex plays a crucial role in routing of TRPV5 and TRPV6 to plasma membrane.
Mots-clé
Animals
Annexin A2/metabolism
Base Sequence
Calcitriol/metabolism
Calcium Channels/*metabolism
Calcium-Binding Proteins/metabolism
DNA Primers
Epithelium/metabolism
Gene Silencing
Immunohistochemistry
Mice
Protein Binding
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
*S100 Proteins
Two-Hybrid System Techniques
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:03
Dernière modification de la notice
20/08/2019 14:33