C-terminal cytoplasmic region of ATP11C variant determines its localization at the polarized plasma membrane

Journal of Cell Science
Masahiro TakayamaHye-Won Shin

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 previously showed that the C-terminus of ATP11C-a is critical for endocytosis upon PKC activation. On the other hand, ATP11C-b and ATP11C-c did not undergo endocytosis upon PKC activation. Importantly, we 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 at the distinct place of the plasma membrane in polariz...Continue Reading

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Citations

Jul 3, 2020·Molecular Biology of the Cell·Sayuri OkamotoHye-Won Shin
Sep 17, 2021·Journal of Cell Science·Hiroki InoueHye-Won Shin

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