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
Auteur⸱e⸱s
van de Graaf  S. F., Hoenderop  J. G., Gkika  D., Lamers  D., Prenen  J., Rescher  U., Gerke  V., Staub  O., Nilius  B., Bindels  R. J.
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
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
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