title: TMEM16F (Anoctamin 6), an anion channel of delayed Ca(2+) activation.
abstract: Members of the TMEM16 (Anoctamin) family of membrane proteins have been shown to be essential constituents of the Ca(2+)-activated Cl(-) channel (CaCC) in many cell types. In this study, we have investigated the electrophysiological properties of mouse TMEM16F. Heterologous expression of TMEM16F in HEK293 cells resulted in plasma membrane localization and an outwardly rectifying ICl,Ca that was activated with a delay of several minutes. Furthermore, a significant Na(+) current was activated, and the two permeabilities were correlated according to PNa = 0.3 PCl. The current showed an EC50 of 100 µM intracellular free Ca(2+) concentration and an Eisenman type 1 anion selectivity sequence of PSCN > PI > PBr > PCl > PAsp. The mTMEM16F-associated ICl,Ca was abolished in one mutant of the putative pore region (R592E) but retained in two other mutants (K616E and R636E). The mutant K616E had a lower relative permeability to iodide, and the mutant R636E had an altered anion selectivity sequence (PSCN = PI = PBr = PCl > PAsp). Our data provide evidence that TMEM16F constitutes a Ca(2+)-activated anion channel or a pore-forming subunit of an anion channel with properties distinct from TMEM16A.
authors: Department of Biology, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
authors: Søren
authors: S
authors: Grubb
authors: Kristian A
authors: KA
authors: Poulsen
authors: Christian Ammitzbøll
authors: CA
authors: Juul
authors: Tania
authors: T
authors: Kyed
authors: Thomas K
authors: TK
authors: Klausen
authors: Erik Hviid
authors: EH
authors: Larsen
authors: Else K
authors: EK
authors: Hoffmann
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D000075368:Anoctamins; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010539:Permeability; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
chemical_list: C576687:ANO6 protein, mouse; D000838:Anions; D000075368:Anoctamins; D018118:Chloride Channels; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D012964:Sodium; D002118:Calcium
references: J Biol Chem. 2010 Mar 5;285(10):7838-45
references: 20056604
references: Am J Physiol Cell Physiol. 2012 Feb 1;302(3):C482-93
references: 22075693
references: Physiol Rev. 2002 Apr;82(2):503-68
references: 11917096
references: Exp Physiol. 2012 Feb;97(2):184-92
references: 21908539
references: Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18168-72
references: 22006324
references: Dev Biol. 2008 Sep 1;321(1):141-9
references: 18585372
references: Nature. 2008 Oct 30;455(7217):1210-5
references: 18724360
references: Am J Pathol. 2004 Jul;165(1):107-13
references: 15215166
references: J Physiol. 2009 Oct 15;587(Pt 20):4887-904
references: 19687122
references: Blood. 2011 Apr 21;117(16):4399-400
references: 21511967
references: Cancer Res. 2008 Aug 1;68(15):6306-12
references: 18676855
references: Anal Biochem. 2005 Dec 15;347(2):303-15
references: 16289079
references: Biochem Biophys Res Commun. 2005 Jun 17;331(4):1099-106
references: 15882990
references: Cell Calcium. 1997 Jul;22(1):53-63
references: 9232352
references: J Thromb Haemost. 2011 Jul;9 Suppl 1:76-91
references: 21781244
references: J Biol Chem. 2009 May 29;284(22):14875-80
references: 19363029
references: Nature. 2010 Dec 9;468(7325):834-8
references: 21107324
references: Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H97-H104
references: 18441200
references: J Biol Chem. 2009 Oct 16;284(42):28571-8
references: 19654323
references: Biochim Biophys Acta. 1998 Sep 23;1374(1-2):94-106
references: 9814856
references: Am J Physiol Cell Physiol. 2013 Apr 15;304(8):C748-59
references: 23426967
references: J Biol Chem. 2009 Oct 16;284(42):28698-703
references: 19679661
references: Proc Am Thorac Soc. 2004;1(1):22-7
references: 16113407
references: Science. 2008 Oct 24;322(5901):590-4
references: 18772398
references: BMC Evol Biol. 2010 Oct 21;10:319
references: 20964844
references: J Neurosci. 2009 May 27;29(21):6809-18
references: 19474308
references: Mol Cell Proteomics. 2011 Feb;10(2):M110.004697
references: 20974900
references: Acta Physiol (Oxf). 2011 Jul;202(3):435-64
references: 21288306
references: Cell Calcium. 2009 Oct;46(4):233-41
references: 19783045
references: Dev Dyn. 2008 Sep;237(9):2566-74
references: 18729231
references: Gene Expr Patterns. 2009 Mar;9(3):178-91
references: 19059364
references: Channels (Austin). 2008 Jul-Aug;2(4):252-60
references: 18769137
references: Curr Opin Neurobiol. 2003 Aug;13(4):469-75
references: 12965295
references: J Physiol. 2009 May 15;587(Pt 10):2127-39
references: 19015192
references: J Physiol. 1983 Sep;342:309-25
references: 6313909
references: Acta Pharmacol Sin. 2011 Jun;32(6):685-92
references: 21642943
references: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3059-64
references: 14981236
references: Am J Hum Genet. 2004 Nov;75(5):927-8; author reply 928-9
references: 15457408
references: J Biol Chem. 2011 Jan 14;286(2):1381-8
references: 21056985
references: Nat Rev Drug Discov. 2009 Feb;8(2):153-71
references: 19153558
references: Cell. 2008 Sep 19;134(6):1019-29
references: 18805094
references: J Membr Biol. 1998 May 15;163(2):97-110
references: 9592074
references: Physiol Rev. 2009 Jan;89(1):193-277
references: 19126758
references: Acta Physiol Scand. 2003 Feb;177(2):119-47
references: 12558550
references: J Gen Physiol. 2000 Jan;115(1):59-80
references: 10613919
references: Pflugers Arch. 2009 Oct;458(6):1023-38
references: 19475416
references: Exp Physiol. 2012 Feb;97(2):177-83
references: 21984732
references: Circ Res. 2012 Mar 30;110(7):990-9
references: 22394518
references: Exp Physiol. 2012 Feb;97(2):193-9
references: 21890523
references: Chem Senses. 2010 Mar;35(3):239-45
references: 20100788
references: J Gen Physiol. 2006 Jul;128(1):73-87
references: 16801382
references: Pflugers Arch. 2007 Sep;454(6):879-89
references: 17361457
references: Cell. 2012 Sep 28;151(1):111-22
references: 23021219
references: Annu Rev Physiol. 2005;67:719-58
references: 15709976
references: J Neurophysiol. 2003 Dec;90(6):3764-73
references: 12944538
references: EMBO J. 1982;1(11):1307-12
references: 6144542
references: Am J Hum Genet. 2010 Feb 12;86(2):213-21
references: 20096397
references: J Physiol. 1982 Oct;331:253-84
references: 7153904
references: J Cell Physiol. 2007 Mar;210(3):831-42
references: 17111356