RRC ID 67359
Author Segawa K, Kurata S, Nagata S.
Title Human Type IV P-type ATPases That Work as Plasma Membrane Phospholipid Flippases and Their Regulation by Caspase and Calcium.
Journal J Biol Chem
Abstract In plasma membranes, flippases translocate aminophospholipids such as phosphatidylserine and phosphatidylethanolamine from the extracellular to the cytoplasmic leaflet. Mammalian ATP11C, a type IV P-type ATPase, acts as a flippase at the plasma membrane. Here, by expressing 12 human type IV P-type ATPases in ATP11C-deficient cells, we determined that ATP8A2 and ATP11A can also act as plasma membrane flippases. As with ATP11C, ATP8A2 and ATP11A localized to the plasma membrane in a CDC50A-dependent manner. ATP11A was cleaved by caspases during apoptosis, and a caspase-resistant ATP11A blocked apoptotic PtdSer exposure. In contrast, ATP8A2 was not cleaved by caspase, and cells expressing ATP8A2 did not expose PtdSer during apoptosis. Similarly, high Ca(2+) concentrations inhibited the ATP11A and ATP11C PtdSer flippase activity, but ATP8A2 flippase activity was relatively resistant to Ca(2+). ATP11A and ATP11C were ubiquitously expressed in human and mouse adult tissues. In contrast, ATP8A2 was expressed in specific tissues, such as the brain and testis. Thus, ATP8A2 may play a specific role in translocating PtdSer in these tissues.
Volume 291(2)
Pages 762-72
Published 2016-1-8
DOI 10.1074/jbc.M115.690727
PII S0021-9258(20)36209-8
PMID 26567335
PMC PMC4705396
MeSH Adenosine Triphosphatases / chemistry Adenosine Triphosphatases / metabolism* Amino Acid Sequence Animals Apoptosis / drug effects Calcium / pharmacology* Caspase 3 / metabolism* Cell Line Cell Membrane / drug effects Cell Membrane / enzymology* Humans Mice, Inbred C57BL Molecular Sequence Data Phosphatidylserines / metabolism Phospholipid Transfer Proteins / metabolism Subcellular Fractions / drug effects Subcellular Fractions / enzymology Tissue Distribution / drug effects
IF 4.238
DNA material human ATP8A1 (RDB18725) human ATP8A2 (RDB18726) human ATP8B1 (RDB18727) human ATP8B2 (RDB18728) human ATP8B3 (RDB18729) human ATP8B4 (RDB18730) human ATP9A (RDB18731) human ATP9B (RDB18732) human ATP10A (RDB18733) human ATP10B (RDB18734) human ATP10D (RDB18735) human ATP11A (RDB18736) human ATP11B (RDB18737) human ATP11C (RDB18738)