Whitlock, J. M. & Hartzell, H. C. Anoctamins/TMEM16 proteins: chloride channels flirting with lipids and extracellular vesicles. Annu Rev. Physiol. 10, 119–143 (2017).
Bevers, E. M. & Williamson, P. L. Getting to the outer leaflet: physiology of phosphatidylserine exposure at the plasma membrane. Physiol. Rev. 96, 605–645 (2016).
Article CAS PubMed Google Scholar
Sakuragi, T. & Nagata, S. Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-023-00604-z (2023).
Article PubMed PubMed Central Google Scholar
Suzuki, J., Umeda, M., Sims, P. J. & Nagata, S. Calcium-dependent phospholipid scrambling by TMEM16F. Nature 468, 834–838 (2010).
Article CAS PubMed Google Scholar
Malvezzi, M. et al. Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel. Nat. Commun. 4, 2367 (2013).
Falzone, M., Malvezzi, M., Lee, B. C. & Accardi, A. Known structures and unknown mechanisms of TMEM16 scramblases and channels. JGP 150, 933–947 (2018).
Article CAS PubMed PubMed Central Google Scholar
Brunner, J. D., Lim, N. K., Schenck, S., Duerst, A. & Dutzler, R. X-ray structure of a calcium-activated TMEM16 lipid scramblase. Nature 516, 207–212 (2014).
Article CAS PubMed Google Scholar
Suzuki, J., Denning, D. P., Imanishi, E., Horvitz, H. R. & Nagata, S. Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science 341, 403–406 (2013).
Article CAS PubMed Google Scholar
Matoba, K. et al. Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion. Nat. Struct. Mol. Biol. 27, 1185–1193 (2020).
Article CAS PubMed Google Scholar
Maeda, S. et al. Structure, lipid scrambling activity and role in autophagosome formation of ATG9A. Nat. Struct. Mol. Biol. 27, 1194–1201 (2020).
Article CAS PubMed PubMed Central Google Scholar
Guardia, C. M. et al. Structure of Human ATG9A, the only transmembrane protein of the core autophagy machinery. Cell Rep. 31, 107837 (2020).
Article CAS PubMed PubMed Central Google Scholar
Menon, I. et al. Opsin is a phospholipid flippase. Curr. Biol. 21, 149–153 (2011).
Article CAS PubMed PubMed Central Google Scholar
Jahn, H., Bartoš, L., Holthuis, J. C. M., Vácha, R. & Menon, A. K. Mitochondrial phospholipid import mediated by VDAC, a dimeric beta barrel scramblase. Nat. Commun. 14, 8115 (2023).
Anglin, T. C., Brown, K. L. & Conboy, J. C. Phospholipid flip-flop modulated by transmembrane peptides WALP and Melittin. J. Struct. Biol. 168, 37–52 (2009).
Article CAS PubMed PubMed Central Google Scholar
Mihajlovic, M. & Lazaridis, T. Antimicrobial peptides in toroidal and cylindrical pores. Biochim. Biophys. Acta 1798, 1485–1493 (2010).
Article CAS PubMed PubMed Central Google Scholar
Kol, M. A. et al. Phospholipid flop induced by transmembrane peptides in model membranes is modulated by lipid composition. Biochemistry 42, 231–237 (2003).
Article CAS PubMed Google Scholar
Falzone, M. E. et al. Structural basis of Ca2+-dependent activation and lipid transport by a TMEM16 scramblase. eLife 8, e43229 (2019).
Article PubMed PubMed Central Google Scholar
Bushell, S. R. et al. The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K. Nat. Commun. 10, 3956 (2019).
Article PubMed PubMed Central Google Scholar
Feng, S. et al. Cryo-EM studies of TMEM16F calcium-activated ion channel suggest features important for lipid scrambling. Cell Rep. 28, 567–579 (2019).
Straub, M. S., Alvadia, C., Sawicka, M. & Dutzler, R. Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling. eLife 10, e69800 (2021).
Article CAS PubMed PubMed Central Google Scholar
Kalienkova, V. et al. Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM. eLife 8, e44364 (2019).
Article PubMed PubMed Central Google Scholar
Alvadia, C. et al. Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F. eLife 8, e44365 (2019).
Article PubMed PubMed Central Google Scholar
Pomorski, T. & Menon, A. K. Lipid flippases and their biological functions. Cell. Mol. Life Sci. 63, 2908–2921 (2006).
Article CAS PubMed Google Scholar
Bethel, N. P. & Grabe, M. Atomistic insight into lipid translocation by a TMEM16 scramblase. Proc. Natl Acad. Sci. USA 113, 14049–14054 (2016).
Article CAS PubMed PubMed Central Google Scholar
Jiang, T., Yu, K., Hartzell, H. C. & Tajkhorshid, E. Lipids and ions traverse the membrane by the same physical pathway in the nhTMEM16 scramblase. eLife 6, e28671 (2017).
Article PubMed PubMed Central Google Scholar
Yu, K. et al. Identification of a lipid scrambling domain in ANO6/TMEM16F. eLife 4, 1–23 (2015).
Lee, B. C. et al. Gating mechanism of the extracellular entry to the lipid pathway in a TMEM16 scramblase. Nat. Commun. 9, 3251 (2018).
Article PubMed PubMed Central Google Scholar
Kostritskii, A. Y. & Machtens, J.-P. Molecular mechanisms of ion conduction and ion selectivity in TMEM16 lipid scramblases. Nat. Commun. 12, 2826 (2021).
Article CAS PubMed PubMed Central Google Scholar
Arndt, M. et al. Structural basis for the activation of the lipid scramblase TMEM16F. Nat. Commun. 13, 6692 (2022).
Article CAS PubMed PubMed Central Google Scholar
Falzone, M. E. et al. TMEM16 scramblases thin the membrane to enable lipid scrambling. Nat. Commun. 13, 2604 (2022).
Article CAS PubMed PubMed Central Google Scholar
Feng, S. et al. Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase. Nat. Commun. 14, 4874 (2023).
Article CAS PubMed PubMed Central Google Scholar
Jia, Z., Huang, J. & Chen, J. Activation of TMEM16F by inner gate charged mutations and possible lipid/ion permeation mechanisms. Biophys. J. 121, 3445–3457 (2022).
Article CAS PubMed PubMed Central Google Scholar
Khelashvili, G., Kots, E., Cheng, X., Levine, M. V. & Weinstein, H. The allosteric mechanism leading to an open-groove lipid conductive state of the TMEM16F scramblase. Commun. Biol. 5, 990 (2022).
Article CAS PubMed PubMed Central Google Scholar
Ritchie, T. K., et al. Methods in Enzymology (Elsevier, 2009).
Grinkova, Y. V., Denisov, I. G. & Sligar, S. G. Engineering extended membrane scaffold proteins for self-assembly of soluble nanoscale lipid bilayers. Protein Eng. Des. Sel. 23, 843–848 (2010).
Article CAS PubMed PubMed Central Google Scholar
Lim, N. K., Lam, A. K. M. & Dutzler, R. Independent activation of ion conduction pores in the double-barreled calcium-activated chloride channel TMEM16A. J. Gen. Physiol. 148, 375–392 (2016).
Article CAS PubMed PubMed Central Google Scholar
Jeng, G., Aggarwal, M., Yu, W.-P. & Chen, T.-Y. Independent activation of distinct pores in dimeric TMEM16A channels. J. Gen. Physiol. 148, 393–404 (2016).
Article CAS PubMed PubMed Central Google Scholar
Khelashvili, G. et al. Dynamic modulation of the lipid translocation groove generates a conductive ion channel in Ca2+-bound nhTMEM16. Nat. Commun. 10, 4972 (2019).
Article PubMed PubMed Central Google Scholar
Lee, B.-C., Menon, AnantK. & Accardi, A. The nhTMEM16 scramblase is also a nonselective ion channel. Biophys. J. 111, 1919–1924 (2016).
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