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TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation.
Yang H
,
Kim A
,
David T
,
Palmer D
,
Jin T
,
Tien J
,
Huang F
,
Cheng T
,
Coughlin SR
,
Jan YN
,
Jan LY
.
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Collapse of membrane lipid asymmetry is a hallmark of blood coagulation. TMEM16F of the TMEM16 family that includes TMEM16A/B Ca(2+)-activated Cl(-) channels (CaCCs) is linked to Scott syndrome with deficient Ca(2+)-dependent lipid scrambling. We generated TMEM16F knockout mice that exhibit bleeding defects and protection in an arterial thrombosis model associated with platelet deficiency in Ca(2+)-dependent phosphatidylserine exposure and procoagulant activity and lack a Ca(2+)-activated cation current in the platelet precursor megakaryocytes. Heterologous expression of TMEM16F generates a small-conductance Ca(2+)-activated nonselective cation (SCAN) current with subpicosiemens single-channel conductance rather than a CaCC. TMEM16F-SCAN channels permeate both monovalent and divalent cations, including Ca(2+), and exhibit synergistic gating by Ca(2+) and voltage. We further pinpointed a residue in the putative pore region important for the cation versus anion selectivity of TMEM16F-SCAN and TMEM16A-CaCC channels. This study thus identifies a Ca(2+)-activated channel permeable to Ca(2+) and critical for Ca(2+)-dependent scramblase activity during blood coagulation. PAPERFLICK:
Almaça,
TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A.
2009, Pubmed
Almaça,
TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A.
2009,
Pubmed
Ayoub,
ANO1 amplification and expression in HNSCC with a high propensity for future distant metastasis and its functions in HNSCC cell lines.
2010,
Pubmed
Bevers,
Phospholipid scramblase: an update.
2010,
Pubmed
Bevers,
Changes in membrane phospholipid distribution during platelet activation.
1983,
Pubmed
Caputo,
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
2008,
Pubmed
Castoldi,
Compound heterozygosity for 2 novel TMEM16F mutations in a patient with Scott syndrome.
2011,
Pubmed
Contreras,
Transbilayer (flip-flop) lipid motion and lipid scrambling in membranes.
2010,
Pubmed
Duran,
ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins.
2012,
Pubmed
Frings,
Neuronal Ca2+ -activated Cl- channels--homing in on an elusive channel species.
2000,
Pubmed
Furie,
Mechanisms of thrombus formation.
2008,
Pubmed
Gurtovenko,
Defect-mediated trafficking across cell membranes: insights from in silico modeling.
2010,
Pubmed
Hartzell,
Calcium-activated chloride channels.
2005,
Pubmed
Hofmann,
TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel.
2003,
Pubmed
Huang,
Calcium-activated chloride channels (CaCCs) regulate action potential and synaptic response in hippocampal neurons.
2012,
Pubmed
Launay,
TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.
2002,
Pubmed
Magleby,
Gating mechanism of BK (Slo1) channels: so near, yet so far.
2003,
Pubmed
Mahaut-Smith,
Patch-clamp recordings of electrophysiological events in the platelet and megakaryocyte.
2004,
Pubmed
Mahaut-Smith,
The P2X1 receptor and platelet function.
2011,
Pubmed
Martins,
Anoctamin 6 is an essential component of the outwardly rectifying chloride channel.
2011,
Pubmed
Menon,
Opsin is a phospholipid flippase.
2011,
Pubmed
Nilius,
Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b.
2004,
Pubmed
Peña,
Non-selective cation channel blockers: potential use in nervous system basic research and therapeutics.
2008,
Pubmed
Pomorski,
Lipid flippases and their biological functions.
2006,
Pubmed
Prawitt,
TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i.
2003,
Pubmed
Rosing,
The role of activated human platelets in prothrombin and factor X activation.
1985,
Pubmed
Sanyal,
Flipping lipids: why an' what's the reason for?
2009,
Pubmed
Schreiber,
Expression and function of epithelial anoctamins.
2010,
Pubmed
Schroeder,
Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
2008,
Pubmed
,
Xenbase
Segawa,
Constitutive exposure of phosphatidylserine on viable cells.
2011,
Pubmed
Stanich,
Ano1 as a regulator of proliferation.
2011,
Pubmed
Suzuki,
Calcium-dependent phospholipid scrambling by TMEM16F.
2010,
Pubmed
Ullrich,
Comparison of functional properties of the Ca2+-activated cation channels TRPM4 and TRPM5 from mice.
2005,
Pubmed
van Meer,
Dynamic transbilayer lipid asymmetry.
2011,
Pubmed
Varga-Szabo,
STIM and Orai in platelet function.
2011,
Pubmed
Weiss,
Isolated deficiency of platelet procoagulant activity.
1979,
Pubmed
Williamson,
Transbilayer phospholipid movements in ABCA1-deficient cells.
2007,
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
Zwaal,
Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids.
2004,
Pubmed
