Research progress on TMEM16F and related diseases

doi:10.3969/j.issn.1673-8640.2017.09.019

Abstract

Abstract:

Transmembrane protein 16F（TMEM16F）,also called Anoctamin（ANO）6,is a member of Anoctamin family,which is expressed in many types of cells. At present,the major functions of TMEM16F that have been demonstrated include：（1） Ca²⁺-dependent Cl^- channel,which takes part in the regulation of cell volume;（2） Ca²⁺-regulated nonselective cation channel;（3） Ca²⁺-dependent phospholipid scramblase,which takes part in coagulation,cell apoptosis,bone mineralization and so on. Hence,at the basis of these functions,TMEM16F gene mutation is closely related with Scott syndrome,a rare inherit bleeding disease. The defect of TMEM16F can cause the dysfunction of bone mineralization and cell volume regulation. This review focuses on the structure and functions of TMEM16F,so as to show the role of TMEM16F in the physiopathologic mechanism,diagnosis and treatment of related diseases.

Key words: Transmembrane protein 16F, Ion channel, Phospholipid scramblase

CLC Number:

R446.1

WANG Chanjuan, ZHANG Jie, QIAO Rui. Research progress on TMEM16F and related diseases[J]. Laboratory Medicine, 2017, 32(9): 831-836.

References 39

[1]	YANG Y D,CHO H,KOO J Y,et al.TMEM16A confers receptor-activated calcium-dependent chloride conductance[J]. Nature,2008,455(7217):1210-1215.
[2]	YU K,DURAN C,QU Z,et al.Explaining calcium-dependent gating of anoctamin-1 chloride channels requires a revised topology[J]. Circ Res,2012,110(7):990-999.
[3]	YANG H,KIM A,DAVID T,et al.TMEM16F forms a Ca2+ -activated cation channel required for lipid scrambling in platelets during blood coagulation[J]. Cell,2012,151(1):111-122.
[4]	KUNZELMANN K,TIAN Y,MARTINS J R,et al.Anoctamins[J]. Pflugers Arch,2011,462(2):195-208.
[5]	KUNZELMANN K,SCHREIBER R,KMIT A,et al.Expression and function of epithelial anoctamins[J]. Exp Physiol,2012,97(2):184-192.
[6]	MALVEZZI M,CHALAT M,JANJUSEVIC R,et al.Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel[J]. Nat Commun,2013,4:2367.
[7]	TIAN Y,SCHREIBER R,KUNZELMANN K.Anoctamins are a family of Ca2+-activated Cl- channels[J]. J Cell Sci,2012,125(Pt 21):4991-4998.
[8]	KMIT A,VAN KRUCHTEN R,OUSINGSAWAT J,et al.Calcium-activated and apoptotic phospholipid scrambling induced by Ano6 can occur independently of Ano6 ion currents[J]. Cell Death Dis,2013,4:e611.
[9]	VIITANEN T M,SUKUMARAN P,LÖF C,et al. Functional coupling of TRPC2 cation channels and the calcium-activated anion channels in rat thyroid cells:implications for iodide homeostasis[J]. J Cell Physiol,2013,228(4):814-823.
[10]	MARTINS J R,FARIA D,KONGSUPHOL P,et al.Anoctamin 6 is an essential component of the outwardly rectifying chloride channel[J]. Proc Natl Acad Sci U S A,2011,108(44):18168-18172.
[11]	AGUIRRE A,SHOJI K F,SÁEZ J C,et al. FasL-triggered death of Jurkat cells requires caspase 8-induced,ATP-dependent cross-talk between Fas and the purinergic receptor P2X(7)[J]. J Cell Physiol,2013,228(2):485-493.
[12]	SCUDIERI P,CACI E,VENTURINI A,et al.Ion channel and lipid scramblase activity associated with expression of TMEM16F/ANO6 isoforms[J]. J Physiol,2015,593(17):3829-3848.
[13]	BEVERS E M,WILLIAMSON P L.Phospholipid scramblase:an update[J]. FEBS Lett ,2010,584(13):2724-2730.
[14]	HEEMSKERK J W,BEVERS E M,LINDHOUT T.Platelet activation and blood coagulation[J]. Thromb Haemost,2002,88(2):186-193.
[15]	DALE G L.Coated-platelets:an emerging component of the procoagulant response[J]. J Thromb Haemost,2005,3(10):2185-2192.
[16]	DASGUPTA S K,ARGAIZ E R,MERCADO J E,et al.Platelet senescence and phosphatidylserine exposure[J]. Transfusion,2010,50(10):2167-2175.
[17]	FUJII T,SAKATA A,NISHIMURA S,et al.TMEM16F is required for phosphatidylserine exposure and microparticle release in activated mouse platelets[J]. Proc Natl Acad Sci U S A,2015,112(41):12800-12805.
[18]	KUNZELMANN K,NILIUS B,OWSIANIK G,et al.Molecular functions of anoctamin 6(TMEM16F):a chloride channel,cation channel,or phospholipid scramblase?[J]. Pflugers Arch,2014,466(3):407-414.
[19]	VAN KRUCHTEN R,MATTHEIJ N J,SAUNDERS C,et al.Both TMEM16F-dependent and TMEM16F-independent pathways contribute to phosphatidylserine exposure in platelet apoptosis and platelet activation[J]. Blood,2013,121(10):1850-1857.
[20]	WILLIAMSON P,CHRISTIE A,KOHLIN T,et al.Phospholipid scramblase activation pathways in lymphocytes[J]. Biochemistry,2001,40(27):8065-8072.
[21]	SCHOENWAELDER S M,YUAN Y,JOSEFSSON E C,et al.Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function[J]. Blood,2009,114(3):663-666.
[22]	SEGAWA K,KURATA S,YANAGIHASHI Y,et al.Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure[J]. Science,2014,344(6188):1164-1168.
[23]	YU K,WHITLOCK J M,LEE K,et al.Identification of a lipid scrambling domain in ANO6/TMEM16F[J]. Elife,2015,4:e06901.
[24]	YANG H,KIM A,DAVID T,et al.TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation[J]. Cell,2012,151(1):111-122.
[25]	MUNNIX I C,HARMSMA M,GIDDINGS J C,et al.Store-mediated calcium entry in the regulation of phosphatidylserine exposure in blood cells from Scott patients[J]. Thromb Haemost,2003,89(4):687-695.
[26]	SUZUKI J,UMEDA M,SIMS P J,et al.Calcium-dependent phospholipid scrambling by TMEM16F[J]. Nature,2010,468(7325):834-838.
[27]	MATTHEIJ N J,BRAUN A,VAN KRUCHTEN R,et al.Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling,swelling,and protein cleavage[J]. FASEB J,2016,30(2):727-737.
[28]	HALLIEZ M,FOUASSIER M,ROBILLARD N,et al.Detection of phosphatidyl serine on activated platelets' surface by flow cytometry in whole blood:a simpler test for the diagnosis of Scott syndrome[J]. Br J Haematol, 2015. [Epub ahead of print]
[29]	TSUTSUMI S,KAMATA N,VOKES T J,et al.The novel gene encoding a putative transmembrane protein is mutated in gnathodiaphyseal dysplasia(GDD)[J]. Am J Hum Genet,2004,74(6):1255-1261.
[30]	EHLEN H W,CHINENKOVA M,MOSER M,et al.Inactivation of anoctamin-6/Tmem16f,a regulator of phosphatidylserine scrambling in osteoblasts,leads to decreased mineral deposition in skeletal tissues[J]. J Bone Miner Res,2013,28(2):246-259.
[31]	DAMEK-POPRAWA M,GOLUB E,OTIS L,et al.Chondrocytes utilize a cholesterol-dependent lipid translocator to externalize phosphatidylserine[J]. Biochemistry,2006,45(10):3325-3336.
[32]	HOFFMANN E K,LAMBERT I H,PEDERSEN S F.Physiology of cell volume regulation in vertebrates[J]. Physiol Rev,2009,89(1):193-277.
[33]	VOSS F K,ULLRICH F,MÜNCH J,et al. Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC[J]. Science,2014,344(6184):634-638.
[34]	SIRIANANT L,OUSINGSAWAT J,WANITCHAKOOL P,et al.Cellular volume regulation by anoctamin 6:Ca2+,phospholipaseA2 and osmosensing[J]. Pflugers Arch,2016 ,468(2):335-349.
[35]	PEDERSEN S,LAMBERT I H,THOROED S M,et al.Hypotonic cell swelling induces translocation of the alpha isoform of cytosolic phospholipase A2 but not the gamma isoform in Ehrlich ascites tumor cells[J]. Eur J Biochem,2000,267(17):5531-5539.
[36]	FAN C W,CHEN C Y,CHEN K T,et al.Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivo[J]. J Transl Med,2012,10:254.
[37]	KATO U,INADOME H,YAMAMOTO M,et al.Role for phospholipid flippase complex of ATP8A1 and CDC50A proteins in cell migration[J]. J Biol Chem,2013,288(7):4922-4934.
[38]	JACOBSEN K S,ZEEBERG K,SAUTER D R,et al.The role of TMEM16A(ANO1)and TMEM16F(ANO6)in cell migration[J]. Pflugers Arch,2013,465(12):1753-1762.
[39]	KIM H J,JUN I,YOON J S,et al.Selective serotonin reuptake inhibitors facilitate ANO6(TMEM16F)current activation and phosphatidylserine exposure[J]. Pflugers Arch,2015,467(11):2243-2256.