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  • Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex
  • van de Graaf SF; Hoenderop JG; Gkika D; Lamers D; Prenen J; Rescher U; Gerke V; Staub O; Nilius B; Bindels RJ
  • EMBO J 2003[Apr]; 22 (7): 1478-87
  • 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.
  • |*S100 Proteins[MESH]
  • |Animals[MESH]
  • |Annexin A2/metabolism[MESH]
  • |Base Sequence[MESH]
  • |Calcitriol/metabolism[MESH]
  • |Calcium Channels/*metabolism[MESH]
  • |Calcium-Binding Proteins/metabolism[MESH]
  • |DNA Primers[MESH]
  • |Epithelium/metabolism[MESH]
  • |Gene Silencing[MESH]
  • |Immunohistochemistry[MESH]
  • |Mice[MESH]
  • |Protein Binding[MESH]
  • |RNA Interference[MESH]
  • |Reverse Transcriptase Polymerase Chain Reaction[MESH]
  • |Two-Hybrid System Techniques[MESH]





  • *{{pmid12660155}}
    *<b>[http://www.kidney.de/mlpefetch.php?search=12660155 Functional expression of the epithelial Ca(2+) channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex ]</b> EMBO J 2003; 22(7) ; 1478-87 van de Graaf SF; Hoenderop JG; Gkika D; Lamers D; Prenen J; Rescher U; Gerke V; Staub O; Nilius B; Bindels RJ

        *12660155*

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    EMBO J

    1478 7.22 2003