Anoctamin-6 Controls Bone Mineralization by Activating the Calcium Transporter NCX1

A TMEM16F point mutation causes an absence of canine platelet TMEM16F and ineffective activation and death‐induced phospholipid scrambling

“…Unlike TMEM16A, however, we did not find an apparent association of TMEM16F with the ezrin–radixin–moesin network of signaling and scaffold proteins. The calcium transporter, NCX1, has previously been described as a binding partner of TMEM16F in osteoblasts . We did not identify NCX1 in the canine platelet proteome, but CLIC1, a chloride channel with a regulatory role in osteoblast differentiation , was detected.…”

Critical Role of Lipid Scramblase TMEM16F in Phosphatidylserine Exposure and Repair of Plasma Membrane after Pore Formation

“…Loss of TMEM16F had no effect on T cell development or distribution of lymphoid subsets, as described previously (Hu et al, 2016;Figures S2A and S2B). However, as documented elsewhere (Fujii et al, 2015;Ousingsawat et al, 2015;Yang et al, 2012), it caused abnormal clot formation in vitro (reduced ''clot rate'') and reduced embryonic or perinatal viability (Figures S2C and S2D). TMEM16F deficiency in mice has also been reported to cause a bone mineralization defect (Ousingsawat et al, 2015), although we did not test this phenotype in our mouse strain.…”

Molecular underpinning of intracellular pH regulation on TMEM16F

“…As one of the most studied TMEM16 proteins, TMEM16F is a dual functional Ca 2+ -activated non-selective ion channel and Ca 2+ -activated phospholipid scramblase (CaPLSase), which mediates phospholipids flip-flop across membrane lipid bilayer and rapidly destroy the asymmetric distribution of phospholipids on cell membranes (Suzuki et al ., 2010; Yang et al ., 2012). TMEM16F-mediated cell surface exposure of phosphatidylserine (PS), an amino-phospholipid concentrated in the inner leaflet of the plasma membrane, is essential for a number of cellular and physiological processes including blood coagulation (Suzuki et al ., 2010; Yang et al ., 2012), skeleton development (Ehlen et al ., 2013; Ousingsawat et al ., 2015), viral infection (Zaitseva et al ., 2017), membrane microparticle release (Fujii et al ., 2015), cell-cell fusion and placental development (Zhang et al ., 2020). The loss-of-function mutations of human TMEM16F cause Scott Syndrome, a mild bleeding disorder characterized by a deficiency in CaPLSase-mediated PS exposure and subsequent defects on prothrombinase assembly, thrombin generation and blood coagulation (Suzuki et al ., 2010; Castoldi et al ., 2011).…”