Substrates of P4‐ATPases: beyond aminophospholipids (phosphatidylserine and phosphatidylethanolamine). Issue 3 (3rd December 2018)

• Record Type: Journal Article
• Authors: Shin, Hye-Won; Takatsu, Hiroyuki
• Is Part Of: FASEB journal. Volume 33:Issue 3(2019)
• Page Start: 3087
• Page End: 3096
• Publication Date: 2018-12-03
• Subjects: flippase -- lipid bilayer -- asymmetry -- biological membrane -- membrane curvature; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201801873R
• Languages: English
• ISSNs: 0892-6638

Abstract

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). FASEB J. 33, 3087–3096 (2019). www.fasebj.org