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Membrane Asymmetry and Phospholipid Translocases in Eukaryotic Cells

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Abstract

Membranes provide an essential physical boundary to the cell, allowing separation of a living cell from its environment, as well as subcellular compartmentalization of functional organelles in eukaryotic cells. Each membrane has a unique lipid and protein composition, which is optimized for its function as the interface between the extracellular and intracellular environments. As the primary structural component of this interface, phospholipids form the membrane bilayer backbone, and provide the major barrier function and other functions such as signal transduction and molecular recognition. One crucial feature of membrane phospholipids is their asymmetrical distribution between the two leaflets in various cell membranes, which appears to be a common theme from yeast to human cells. For example, in the plasma membrane of red blood cells, the extracellular leaflet is predominantly occupied by phosphatidylcholine (PtdCho) and sphingomyelin (SM), while the cytosolic leaflet is enriched in phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn). The asymmetric distribution of membrane lipids and their regulated transbilayer movement plays important roles in many cellular processes and functions, including apoptosis, blood coagulation and cell membrane integrity. But how is membrane lipid asymmetry generated and maintained? More specifically, how do phospholipids traverse the membrane bilayer, known as flip-flop, in a living cell? Since phospholipids are amphipathic molecules with large polar groups, their movement across the hydrophobic membrane interior is thermodynamically unfavorable. Experimental evidence demonstrates that in biological membranes, this process is mediated and facilitated by a number of membrane proteins, which function as phospholipid translocases that include P4-ATPases, ATP-binding cassette (ABC) transporters, TMEM16 family members, and others. Furthermore, recent advancement of structural studies on some of these proteins starts to shed light on the molecular mechanisms of phospholipid translocation by lipid translocases. In this chapter, we review our knowledge on phospholipid translocases in eukaryotic cells, and discuss our current understanding toward their functions and mechanisms.

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Fan, J., Wang, X., Sun, Z., Zhou, X. (2018). Membrane Asymmetry and Phospholipid Translocases in Eukaryotic Cells. In: Cao, Y. (eds) Advances in Membrane Proteins. Springer, Singapore. https://doi.org/10.1007/978-981-13-0532-0_3

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