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Title: Phospholipid Flippase ATP10A Translocates Phosphatidylcholine and Is Involved in Plasma Membrane Dynamics.
Authors: Naito, Tomoki
Takatsu, Hiroyuki
Miyano, Rie
Takada, Naoto
Nakayama, Kazuhisa  kyouindb  KAKEN_id  orcid (unconfirmed)
Shin, Hye-Won  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 申, 惠媛
Keywords: ATPase
lipid bilayer
membrane protein
plasma membrane
cell spreading
Issue Date: 12-Jun-2015
Publisher: American Society for Biochemistry and Molecular Biology
Journal title: The Journal of biological chemistry
Volume: 290
Issue: 24
Start page: 15004
End page: 15017
Abstract: We showed previously that ATP11A and ATP11C have flippase activity toward aminophospholipids (phosphatidylserine (PS) and phosphatidylethanolamine (PE)) and ATP8B1 and that ATP8B2 have flippase activity toward phosphatidylcholine (PC) (Takatsu, H., Tanaka, G., Segawa, K., Suzuki, J., Nagata, S., Nakayama, K., and Shin, H. W. (2014) J. Biol. Chem. 289, 33543-33556). Here, we show that the localization of class 5 P4-ATPases to the plasma membrane (ATP10A and ATP10D) and late endosomes (ATP10B) requires an interaction with CDC50A. Moreover, exogenous expression of ATP10A, but not its ATPase-deficient mutant ATP10A(E203Q), dramatically increased PC flipping but not flipping of PS or PE. Depletion of CDC50A caused ATP10A to be retained at the endoplasmic reticulum instead of being delivered to the plasma membrane and abrogated the increased PC flipping activity observed by expression of ATP10A. These results demonstrate that ATP10A is delivered to the plasma membrane via its interaction with CDC50A and, specifically, flips PC at the plasma membrane. Importantly, expression of ATP10A, but not ATP10A(E203Q), dramatically altered the cell shape and decreased cell size. In addition, expression of ATP10A, but not ATP10A(E203Q), delayed cell adhesion and cell spreading onto the extracellular matrix. These results suggest that enhanced PC flipping activity due to exogenous ATP10A expression alters the lipid composition at the plasma membrane, which may in turn cause a delay in cell spreading and a change in cell morphology.
Rights: This research was originally published in [The Journal of Biological Chemistry, 290, 15004-15017. doi: 10.1074/jbc.M115.655191] © the American Society for Biochemistry and Molecular Biology
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
DOI(Published Version): 10.1074/jbc.M115.655191
PubMed ID: 25947375
Appears in Collections:Journal Articles

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