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Substrates of P4-ATPases: Beyond Aminophospholipids (Phosphatidylserine and Phosphatidylethanolamine)

Substrates of P4-ATPases: Beyond Aminophospholipids (Phosphatidylserine and Phosphatidylethanolamine)

Hye-Won Shin, Hiroyuki Takatsu

FASEB J. 2019 Mar;33(3):3087-3096.

PMID: 30509129

Abstract:

P4-ATPases, a subfamily of P-type ATPases, were initially identified as aminophospholipid translocases in eukaryotic membranes. These proteins generate and maintain membrane lipid asymmetry by translocating aminophospholipids (phosphatidylserine and phosphatidylethanolamine) from the exoplasmic/lumenal leaflet to the cytoplasmic leaflet. The human genome encodes 14 P4-ATPases, and the cellular localizations, substrate specificities, and cellular roles of these proteins were recently revealed. Numerous P4-ATPases, including ATP8A1, ATP8A2, ATP11A, ATP11B, and ATP11C, transport phosphatidylserine. By contrast, ATP8B1, ATP8B2, and ATP10A transport phosphatidylcholine but not aminophospholipids, although there is a discrepancy regarding the substrate of ATP8B1 in the literature. Some yeast and plant P4-ATPases can also translocate phosphatidylcholine. At least 2 P4-ATPases (ATP8A2 and ATP8B1) are associated with severe human diseases, and other P4-ATPases are implicated in various pathophysiologic conditions in mouse models. Here, we discuss the cellular functions of phosphatidylcholine flippases and suggest a model for the phenotype of progressive familial intrahepatic cholestasis 1 caused by a defect in ATP8B1.-Shin, H.-W., Takatsu, H. Substrates of P4-ATPases: beyond aminophospholipids (phosphatidylserine and phosphatidylethanolamine).

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP39382086-A	Phosphatidylethanolamine		39382-08-6	Price

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