Functional expression of the epithelial Ca2+ channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex

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 a...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2003-04, Vol.22 (7), p.1478-1487
Main Authors: van de Graaf, Stan F.J., Hoenderop, Joost G.J., Gkika, Dimitra, Lamers, Dennis, Prenen, Jean, Rescher, Ursula, Gerke, Volker, Staub, Olivier, Nilius, Bernd, Bindels, René J.M.
Format: Article
Language:English
Subjects:
Amino acids
CaT1
ECaC
EMBO20
Life Sciences
p11
PDZ motif
siRNA
Yeasts
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c5062-556925780c9b2f34d9f4937c615c7ba7e167d1781cba5f5985ed76c60bef5c473
cites
container_end_page 1487
container_issue 7
container_start_page 1478
container_title The EMBO journal
container_volume 22
creator van de Graaf, Stan F.J.
Hoenderop, Joost G.J.
Gkika, Dimitra
Lamers, Dennis
Prenen, Jean
Rescher, Ursula
Gerke, Volker
Staub, Olivier
Nilius, Bernd
Bindels, René J.M.
description 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.
doi_str_mv 10.1093/emboj/cdg162
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_152906</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>347679471</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5062-556925780c9b2f34d9f4937c615c7ba7e167d1781cba5f5985ed76c60bef5c473</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhiMEotvCjR9gcaKC0LET2_GBw7L9WKoFCi1wtBzH2fWSTVI7KdsD_x2HrKqCEPJhbM_7vDP2RNEzDK8xiOTIbPJmfaSLJWbkQTTBKYOYAKcPowkQhuMUZ2Iv2vd-DQA04_hxtIcJY4ApnUQ_T_tad7apVYXMtnXG-3BATYm6lUGmtSFUNiRnirxEeqXq2lQevbj6fPGVIlUXaNixQ-TMdW8DjpT3jbaqu2dziQGmGOIB3toaEaSbTVuZ7ZPoUakqb57u4kH05fTkajaPFx_P3s2mi1hTYCSmlAlCeQZa5KRM0kKUqUi4ZphqnituMOMF5hnWuaIlFRk1BWeaQW5KqlOeHERvRt-2zzem0KbunKpk6-xGuVvZKCv_zNR2JZfNjcSUCGCBPxz51V_UfLqQwx2kYQHPbnDQPt_Vcs11b3wn103vwv96iQUNz0izoaFXo0i7xntnyjtXDHIYq_w9VjmONcjpKP9hK3P7X608ef_2nFNBgQ9cPHI-IPXSuHu9_LvOTm99Z7Z3dZT7LhlPOJXfPpxJfEzOYX75SV4kvwBEgcQL</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>195257487</pqid></control><display><type>article</type><title>Functional expression of the epithelial Ca2+ channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex</title><source>PubMed Central（OA）</source><creator>van de Graaf, Stan F.J. ; Hoenderop, Joost G.J. ; Gkika, Dimitra ; Lamers, Dennis ; Prenen, Jean ; Rescher, Ursula ; Gerke, Volker ; Staub, Olivier ; Nilius, Bernd ; Bindels, René J.M.</creator><creatorcontrib>van de Graaf, Stan F.J. ; Hoenderop, Joost G.J. ; Gkika, Dimitra ; Lamers, Dennis ; Prenen, Jean ; Rescher, Ursula ; Gerke, Volker ; Staub, Olivier ; Nilius, Bernd ; Bindels, René J.M.</creatorcontrib><description>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.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/cdg162</identifier><identifier>PMID: 12660155</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley &amp; Sons, Ltd</publisher><subject>Amino acids ; CaT1 ; ECaC ; EMBO20 ; Life Sciences ; p11 ; PDZ motif ; siRNA ; Yeasts</subject><ispartof>The EMBO journal, 2003-04, Vol.22 (7), p.1478-1487</ispartof><rights>European Molecular Biology Organization 2003</rights><rights>Copyright © 2003 European Molecular Biology Organization</rights><rights>Copyright Oxford University Press(England) Apr 01, 2003</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2003 European Molecular Biology Organization 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5062-556925780c9b2f34d9f4937c615c7ba7e167d1781cba5f5985ed76c60bef5c473</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC152906/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC152906/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://hal.univ-lille.fr/hal-04040078$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>van de Graaf, Stan F.J.</creatorcontrib><creatorcontrib>Hoenderop, Joost G.J.</creatorcontrib><creatorcontrib>Gkika, Dimitra</creatorcontrib><creatorcontrib>Lamers, Dennis</creatorcontrib><creatorcontrib>Prenen, Jean</creatorcontrib><creatorcontrib>Rescher, Ursula</creatorcontrib><creatorcontrib>Gerke, Volker</creatorcontrib><creatorcontrib>Staub, Olivier</creatorcontrib><creatorcontrib>Nilius, Bernd</creatorcontrib><creatorcontrib>Bindels, René J.M.</creatorcontrib><title>Functional expression of the epithelial Ca2+ channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><description>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.</description><subject>Amino acids</subject><subject>CaT1</subject><subject>ECaC</subject><subject>EMBO20</subject><subject>Life Sciences</subject><subject>p11</subject><subject>PDZ motif</subject><subject>siRNA</subject><subject>Yeasts</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhiMEotvCjR9gcaKC0LET2_GBw7L9WKoFCi1wtBzH2fWSTVI7KdsD_x2HrKqCEPJhbM_7vDP2RNEzDK8xiOTIbPJmfaSLJWbkQTTBKYOYAKcPowkQhuMUZ2Iv2vd-DQA04_hxtIcJY4ApnUQ_T_tad7apVYXMtnXG-3BATYm6lUGmtSFUNiRnirxEeqXq2lQevbj6fPGVIlUXaNixQ-TMdW8DjpT3jbaqu2dziQGmGOIB3toaEaSbTVuZ7ZPoUakqb57u4kH05fTkajaPFx_P3s2mi1hTYCSmlAlCeQZa5KRM0kKUqUi4ZphqnituMOMF5hnWuaIlFRk1BWeaQW5KqlOeHERvRt-2zzem0KbunKpk6-xGuVvZKCv_zNR2JZfNjcSUCGCBPxz51V_UfLqQwx2kYQHPbnDQPt_Vcs11b3wn103vwv96iQUNz0izoaFXo0i7xntnyjtXDHIYq_w9VjmONcjpKP9hK3P7X608ef_2nFNBgQ9cPHI-IPXSuHu9_LvOTm99Z7Z3dZT7LhlPOJXfPpxJfEzOYX75SV4kvwBEgcQL</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>van de Graaf, Stan F.J.</creator><creator>Hoenderop, Joost G.J.</creator><creator>Gkika, Dimitra</creator><creator>Lamers, Dennis</creator><creator>Prenen, Jean</creator><creator>Rescher, Ursula</creator><creator>Gerke, Volker</creator><creator>Staub, Olivier</creator><creator>Nilius, Bernd</creator><creator>Bindels, René J.M.</creator><general>John Wiley &amp; Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><general>EMBO Press</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>1XC</scope><scope>5PM</scope></search><sort><creationdate>20030401</creationdate><title>Functional expression of the epithelial Ca2+ channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex</title><author>van de Graaf, Stan F.J. ; Hoenderop, Joost G.J. ; Gkika, Dimitra ; Lamers, Dennis ; Prenen, Jean ; Rescher, Ursula ; Gerke, Volker ; Staub, Olivier ; Nilius, Bernd ; Bindels, René J.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5062-556925780c9b2f34d9f4937c615c7ba7e167d1781cba5f5985ed76c60bef5c473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amino acids</topic><topic>CaT1</topic><topic>ECaC</topic><topic>EMBO20</topic><topic>Life Sciences</topic><topic>p11</topic><topic>PDZ motif</topic><topic>siRNA</topic><topic>Yeasts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van de Graaf, Stan F.J.</creatorcontrib><creatorcontrib>Hoenderop, Joost G.J.</creatorcontrib><creatorcontrib>Gkika, Dimitra</creatorcontrib><creatorcontrib>Lamers, Dennis</creatorcontrib><creatorcontrib>Prenen, Jean</creatorcontrib><creatorcontrib>Rescher, Ursula</creatorcontrib><creatorcontrib>Gerke, Volker</creatorcontrib><creatorcontrib>Staub, Olivier</creatorcontrib><creatorcontrib>Nilius, Bernd</creatorcontrib><creatorcontrib>Bindels, René J.M.</creatorcontrib><collection>Istex</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Earth, Atmospheric &amp; Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest research library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric &amp; Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van de Graaf, Stan F.J.</au><au>Hoenderop, Joost G.J.</au><au>Gkika, Dimitra</au><au>Lamers, Dennis</au><au>Prenen, Jean</au><au>Rescher, Ursula</au><au>Gerke, Volker</au><au>Staub, Olivier</au><au>Nilius, Bernd</au><au>Bindels, René J.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional expression of the epithelial Ca2+ channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><date>2003-04-01</date><risdate>2003</risdate><volume>22</volume><issue>7</issue><spage>1478</spage><epage>1487</epage><pages>1478-1487</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>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.</abstract><cop>Chichester, UK</cop><pub>John Wiley &amp; Sons, Ltd</pub><pmid>12660155</pmid><doi>10.1093/emboj/cdg162</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0261-4189
ispartof The EMBO journal, 2003-04, Vol.22 (7), p.1478-1487
issn 0261-4189
1460-2075
1460-2075
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_152906
source PubMed Central（OA）
subjects Amino acids
CaT1
ECaC
EMBO20
Life Sciences
p11
PDZ motif
siRNA
Yeasts
title Functional expression of the epithelial Ca2+ channels (TRPV5 and TRPV6) requires association of the S100A10-annexin 2 complex
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T12%3A21%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Functional%20expression%20of%20the%20epithelial%20Ca2+%20channels%20(TRPV5%20and%20TRPV6)%20requires%20association%20of%20the%20S100A10-annexin%202%20complex&rft.jtitle=The%20EMBO%20journal&rft.au=van%20de%20Graaf,%20Stan%20F.J.&rft.date=2003-04-01&rft.volume=22&rft.issue=7&rft.spage=1478&rft.epage=1487&rft.pages=1478-1487&rft.issn=0261-4189&rft.eissn=1460-2075&rft.coden=EMJODG&rft_id=info:doi/10.1093/emboj/cdg162&rft_dat=%3Cproquest_pubme%3E347679471%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5062-556925780c9b2f34d9f4937c615c7ba7e167d1781cba5f5985ed76c60bef5c473%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=195257487&rft_id=info:pmid/12660155&rfr_iscdi=true