Anoctamin/TMEM16 Proteins in Lipid Scrambling and Membrane Signaling Restricted; Files & ToC

Whitlock, Jarred M. (Fall 2018)

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The asymmetric organization of membrane lipids is a hallmark of the eukaryotic plasma membrane and is vital for proper cell function. This asymmetry arises from the organization of membrane lipids according to their headgroups via a system of membrane resident lipid transporters and typically results in an extracellular leaflet enriched in phosphatidylcholine and sphingomyelin and a cytosolic leaflet that retains phosphatidylethanolamine and phosphatidylserine. For >35 years it has been recognized that many cells possess the ability to rapidly break down this lipid asymmetry in a Ca2+-dependent manner as a signaling process dubbed phospholipid scrambling. This membrane scrambling exposes cytosolic lipid headgroups (e.g. phosphatidylserine) to the extracellular face, where some are recognized as ligands in cell-cell signaling processes. Recently, members of the anoctamin family of membrane proteins have been recognized for their putative roles in this process. Here I summarize my contribution to the recognition of some anoctamin proteins as phospholipid scramblases, the understanding of how the structure of anoctamins facilitate lipid scrambling, and to the understanding of how anoctamin scramblases regulate biological processes.

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