P4 ATPases--the physiological relevance of lipid flipping transporters.

P4 ATPases are integral transmembrane proteins implicated in phospholipid translocation from the exoplasmic to the cytosolic leaflet of biological membranes. Our present knowledge on the cellular physiology of P4 ATPases is mostly derived from studies in the yeast Saccharomyces cerevisiae, where P4 ATPases play a pivotal role in the biogenesis of intracellular transport vesicles, polarized protein transport and protein maturation. In contrast, the physiological and cellular functions of mammalian P4 ATPases are largely unexplored. P4 ATPases act in concert with members of the CDC50 protein family, which are putative beta-subunits for P4 ATPases. This review highlights the current status of a slowly emerging research field and emphasizes the contribution of P4 ATPases to the vesicle-generating machinery. Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.