Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2012 Jun 26;10926:10376-81. doi: 10.1073/pnas.1200174109.
Show Gene links
Show Anatomy links
Anoctamin 1 (Tmem16A) Ca2+-activated chloride channel stoichiometrically interacts with an ezrin-radixin-moesin network.
Perez-Cornejo P
,
Gokhale A
,
Duran C
,
Cui Y
,
Xiao Q
,
Hartzell HC
,
Faundez V
.
???displayArticle.abstract???
The newly discovered Ca(2+)-activated Cl(-) channel (CaCC), Anoctamin 1 (Ano1 or TMEM16A), has been implicated in vital physiological functions including epithelial fluid secretion, gut motility, and smooth muscle tone. Overexpression of Ano1 in HEK cells or Xenopus oocytes is sufficient to generate Ca(2+)-activated Cl(-) currents, but the details of channel composition and the regulatory factors that control channel biology are incompletely understood. We used a highly sensitive quantitative SILAC proteomics approach to obtain insights into stoichiometric protein networks associated with the Ano1 channel. These studies provide a comprehensive footprint of putative Ano1 regulatory networks. We find that Ano1 associates with the signaling/scaffolding proteins ezrin, radixin, moesin, and RhoA, which link the plasma membrane to the cytoskeleton with very high stoichiometry. Ano1, ezrin, and moesin/radixin colocalize apically in salivary gland epithelial cells, and overexpression of moesin and Ano1 in HEK cells alters the subcellular localization of both proteins. Moreover, interfering RNA for moesin modifies Ano1 current without affecting its surface expression level. Another network associated with Ano1 includes the SNARE and SM proteins VAMP3, syntaxins 2 and -4, and syntaxin-binding proteins munc18b and munc18c, which are integral to translocation of vesicles to the plasma membrane. A number of other regulatory proteins, including GTPases, Ca(2+)-binding proteins, kinases, and lipid-interacting proteins are enriched in the Ano1 complex. These data provide stoichiometrically prioritized information about mechanisms regulating Ano1 function and trafficking to polarized domains of the plasma membrane.
Braun,
Cloning and expression of a calcium-activated chloride channel reveal a novel protein candidate.
2008, Pubmed
Braun,
Cloning and expression of a calcium-activated chloride channel reveal a novel protein candidate.
2008,
Pubmed
Caputo,
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
2008,
Pubmed
Chan,
Annexin IV inhibits calmodulin-dependent protein kinase II-activated chloride conductance. A novel mechanism for ion channel regulation.
1994,
Pubmed
Craige,
Phosphatidylinositol-4-kinase type II alpha contains an AP-3-sorting motif and a kinase domain that are both required for endosome traffic.
2008,
Pubmed
Duran,
Chloride channels: often enigmatic, rarely predictable.
2010,
Pubmed
Duran,
Physiological roles and diseases of Tmem16/Anoctamin proteins: are they all chloride channels?
2011,
Pubmed
Ferrera,
TMEM16A protein: a new identity for Ca(2+)-dependent Cl⁻ channels.
2010,
Pubmed
Flores,
TMEM16 proteins: the long awaited calcium-activated chloride channels?
2009,
Pubmed
,
Xenbase
Galietta,
The TMEM16 protein family: a new class of chloride channels?
2009,
Pubmed
Galindo,
Phylogeny of the TMEM16 protein family: some members are overexpressed in cancer.
2005,
Pubmed
Gokhale,
Quantitative proteomic and genetic analyses of the schizophrenia susceptibility factor dysbindin identify novel roles of the biogenesis of lysosome-related organelles complex 1.
2012,
Pubmed
Hartzell,
Anoctamin/TMEM16 family members are Ca2+-activated Cl- channels.
2009,
Pubmed
Hartzell,
Calcium-activated chloride channels.
2005,
Pubmed
Huang,
Studies on expression and function of the TMEM16A calcium-activated chloride channel.
2009,
Pubmed
Kaetzel,
Annexin VI isoforms are differentially expressed in mammalian tissues.
1994,
Pubmed
Kunzelmann,
Role of the Ca2+ -activated Cl- channels bestrophin and anoctamin in epithelial cells.
2011,
Pubmed
Kunzelmann,
Bestrophin and TMEM16-Ca(2+) activated Cl(-) channels with different functions.
2009,
Pubmed
Kuruma,
Bimodal control of a Ca(2+)-activated Cl(-) channel by different Ca(2+) signals.
2000,
Pubmed
,
Xenbase
Lomant,
Chemical probes of extended biological structures: synthesis and properties of the cleavable protein cross-linking reagent [35S]dithiobis(succinimidyl propionate).
1976,
Pubmed
Mann,
Functional and quantitative proteomics using SILAC.
2006,
Pubmed
Mazzochi,
Interaction of epithelial ion channels with the actin-based cytoskeleton.
2006,
Pubmed
Melvin,
Regulation of fluid and electrolyte secretion in salivary gland acinar cells.
2005,
Pubmed
Muimo,
Regulation of CFTR function by annexin A2-S100A10 complex in health and disease.
2009,
Pubmed
Neisch,
Ezrin, Radixin and Moesin: key regulators of membrane-cortex interactions and signaling.
2011,
Pubmed
Nilius,
Annexin II modulates volume-activated chloride currents in vascular endothelial cells.
1996,
Pubmed
Ong,
Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics.
2002,
Pubmed
Ong,
A practical recipe for stable isotope labeling by amino acids in cell culture (SILAC).
2006,
Pubmed
Ousingsawat,
Loss of TMEM16A causes a defect in epithelial Ca2+-dependent chloride transport.
2009,
Pubmed
Qu,
Characterization of Ca2+-activated Cl- currents in mouse kidney inner medullary collecting duct cells.
2003,
Pubmed
,
Xenbase
Rock,
Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways.
2009,
Pubmed
Romanenko,
Tmem16A encodes the Ca2+-activated Cl- channel in mouse submandibular salivary gland acinar cells.
2010,
Pubmed
Rossin,
Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology.
2011,
Pubmed
Salazar,
Hermansky-Pudlak syndrome protein complexes associate with phosphatidylinositol 4-kinase type II alpha in neuronal and non-neuronal cells.
2009,
Pubmed
Schroeder,
Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
2008,
Pubmed
,
Xenbase
Sheridan,
Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A.
2011,
Pubmed
Südhof,
Membrane fusion: grappling with SNARE and SM proteins.
2009,
Pubmed
Tang,
The cystic fibrosis transmembrane conductance regulator's expanding SNARE interactome.
2011,
Pubmed
Tian,
Calmodulin-dependent activation of the epithelial calcium-dependent chloride channel TMEM16A.
2011,
Pubmed
Trinkle-Mulcahy,
Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes.
2008,
Pubmed
Xiao,
Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop.
2011,
Pubmed
Xie,
Inositol 3,4,5,6-tetrakisphosphate inhibits the calmodulin-dependent protein kinase II-activated chloride conductance in T84 colonic epithelial cells.
1996,
Pubmed
Yang,
TMEM16A confers receptor-activated calcium-dependent chloride conductance.
2008,
Pubmed
,
Xenbase
Yu,
Explaining calcium-dependent gating of anoctamin-1 chloride channels requires a revised topology.
2012,
Pubmed
Zlatic,
Isolation of labile multi-protein complexes by in vivo controlled cellular cross-linking and immuno-magnetic affinity chromatography.
2010,
Pubmed
