Physiological significance of asymmetry of membrane phospholipids

Most eukaryotic cells display clear polarity, indicating the presence of molecular asymmetries. Cell polarity is fundamental to various processes, including differentiation, liferation, and cell morphogenesis. The abnormalities of cell polarity are involved in a variety of diseases. Understanding molecular mechanisms of establishment and maintenance of cell polarity is a very important issue.
In establishing cell polarity, creating specific domains on the plasma membrane and transporting molecules including proteins and lipids to the specific domain via membrane vesicles, are crucial. Cell membranes consist of lipid bilayer and the most abundant membrane lipids are phospholipids. The phospholipid compositions of the two monolayers of the lipid bilayer in most cell membranes are strikingly different, which is called “phospholipid asymmetry”. Phospholipid asymmetry is assumed to be regulated by lipid translocation. However, how phospholipid asymmetry is established and regulated and what role phospholipid asymmetry plays in single cells are largely unknown. Our lab focuses on elucidating the molecular basis underlying the phospholipid asymmetry. We work with yeast Saccharomyces cerevisiae, as a model system, allowing us to make rapid progress on complex problems.

An asymmetric distribution of phospholipids in the plasma membrane is a general feature in eukaryotic cells. Generally, PC and SM primarily located in the exoplasmic leaflet, and PS and PE are in the cytosolic leaflet.
Phospholipid translocases (PLTs) that catalyze the transport of lipid molecules from the exoplasmic to the cytosolic leaflet play a critical role in establishing and maintaining the lipid asymmetry. Recently, PLTs have been demonstrated to consist of a catalytic α subunit of P4 ATPase and regulatory β subunit of a member of the evolutionary conserved Cdc50 protein family.

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