RRC ID 66900
Author Takayama M, Takatsu H, Hamamoto A, Inoue H, Naito T, Nakayama K, Shin HW.
Title The cytoplasmic C-terminal region of the ATP11C variant determines its localization at the polarized plasma membrane.
Journal J Cell Sci
Abstract ATP11C, a member of the P4-ATPase family, is a major phosphatidylserine (PS)-flippase located at the plasma membrane. ATP11C deficiency causes a defect in B-cell maturation, anemia and hyperbilirubinemia. Although there are several alternatively spliced variants derived from the ATP11C gene, the functional differences between them have not been considered. Here, we compared and characterized three C-terminal spliced forms (we designated as ATP11C-a, ATP11C-b and ATP11C-c), with respect to their expression patterns in cell types and tissues, and their subcellular localizations. We had previously shown that the C-terminus of ATP11C-a is critical for endocytosis upon PKC activation. Here, we found that ATP11C-b and ATP11C-c did not undergo endocytosis upon PKC activation. Importantly, we also found that ATP11C-b localized to a limited region of the plasma membrane in polarized cells, whereas ATP11C-a was distributed on the entire plasma membrane in both polarized and non-polarized cells. Moreover, we successfully identified LLXY residues within the ATP11C-b C-terminus as a critical motif for the polarized localization. These results suggest that the ATP11C-b regulates PS distribution in distinct regions of the plasma membrane in polarized cells.
Volume 132(17)
Published 2019-9-2
DOI 10.1242/jcs.231720
PII jcs.231720
PMID 31371488
MeSH 3T3-L1 Cells Adenosine Triphosphatases / metabolism* Amino Acid Sequence Animals Cell Line, Tumor Cell Membrane / metabolism Cell Polarity / physiology Cytoplasm / metabolism Endocytosis Enzyme Activation HCT116 Cells Hep G2 Cells Human Umbilical Vein Endothelial Cells Humans MCF-7 Cells Membrane Transport Proteins / metabolism* Mice Protein Isoforms Protein Kinase C / metabolism RAW 264.7 Cells
IF 4.573
Human and Animal Cells MDA-MB-453(RCB1192)