[Shigekazu Nagata] Asymmetrical distribution of phospholipids at plasma membranes, and its breakdown


Research Director

Shigekazu Nagata

Shigekazu Nagata

Immunology Frontire Research Center,Osaka University
Specially Appointed Professor
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Outline

Phospholipids in the plasma membranes of animal cells are asymmetrically distributed between outer and inner leaflets, by the function of an ATP-dependent enzyme(s), called flippase. Phosphatidylserine and phosphatidylethanolamines are exclusively localized at inner leaflets, while phosphatidylcholine is mainly at outer leaflets. Scramblases that mediate the bi-directional movement of phospholipids break down this asymmetrical distribution in activated platelets and apoptotic cells. The phosphatidylserine thus exposed on the activated platelets provides the scaffold for blood clotting factor, while it works as an “eat me” signal of dead cells for phagocytes. We recently found TMEM16 (8 transmembrane proteins) and XKR family members (6 transmembrane proteins) support Ca2+- or caspase- dependent scrambling of phospholipids, respectively. Whereas, ATP11C, a P4-type ATPase, and its subunit CDC50A were found to work as a flippase. In this project, we plan to determine the structure of these membrane proteins, and elucidate their functional mechanism.

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