Reactome | ANO5, ANO6 expose PS, PE on endothelial cells

ANO5, ANO6 expose PS, PE on endothelial cells

Stable Identifier

R-HSA-9854657

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytoplasmic side of plasma membrane, plasma membrane, external side of plasma membrane

ReviewStatus

3/5

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ANO5, ANO6 expose PS, PE on endothelial cells

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Anoctamin-5 (ANO5, also known as TMEM16E) and ANO6 (TMEM16F) function as a Ca2+-induced phospholipid scramblases to promote procoagulant activity of endothelial cells (EC) (Schmaier AA et al., 2023). ANO5 and ANO6 translocate anionic phospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the inner leaflet to the outer leaflet of the plasma membrane (Lee BC et al., 2018; Feng Z et al., 2024). Structural and functional analyses indicate that activation of the scramblase function of TMEM16s is dependent on Ca²⁺-induced conformational rearrangements in the cytosolic and transmembrane domains (Schreiber R et al, 2018; Falzone ME et al., 2019; Le SC & Yang H 2021; reviewed by Feng Z et al., 2024). Exposed PS (and PE) creates a negatively charged membrane surface, promoting recruitment of factor X (FX) and activation of FX by the TF:FVII complex-mediated cleavage at the EC surfaces (Schmaier AA et al., 2023).

ANO6 (TMEM16F), but not ANO5, catalyzes the exposure of PS and PE at the platelet surface facilitating amplification and propagation of coagulation (Suzuki J et al., 2010)

Literature References

PubMed ID	Title	Journal	Year
36951953	TMEM16E regulates endothelial cell procoagulant activity and thrombosis Schmaier, AA, Anderson, PF, Chen, SM, El-Darzi, E, Aivasovsky, I, Kaushik, MP, Sack, KD, Hartzell, HC, Parikh, SM, Flaumenhaft, R, Schulman, S	J Clin Invest	2023