| First Author | Yang H | Year | 2012 |
| Journal | Cell | Volume | 151 |
| Issue | 1 | Pages | 111-22 |
| PubMed ID | 23021219 | Mgi Jnum | J:188263 |
| Mgi Id | MGI:5440105 | Doi | 10.1016/j.cell.2012.07.036 |
| Citation | Yang H, et al. (2012) TMEM16F Forms a Ca(2+)-Activated Cation Channel Required for Lipid Scrambling in Platelets during Blood Coagulation. Cell 151(1):111-22 |
| abstractText | 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: |
