The C. elegans P4-ATPase TAT-1 regulates lysosome biogenesis and endocytosis |
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Authors: | Ruaud Anne-Françoise Nilsson Lars Richard Fabrice Larsen Morten Krog Bessereau Jean-Louis Tuck Simon |
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Institution: | ENS, Biologie cellulaire de la synapse, Paris, Inserm, U789, Paris, F-75005, France; UmeåCenter for Molecular Pathogenesis, UmeåUniversity, SE-901 87 Umeå, Sweden |
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Abstract: | P-type adenosine triphosphatases (ATPases) of the Drs2p family (P4-ATPases) are multipass transmembrane proteins required to generate and maintain phospholipid asymmetry in membrane bilayers. In Saccharomyces cerevisiae , several members of this family control distinct transport events within the endosomal and secretory pathways. Comparatively, little is known about the functions of P4-ATPases in multicellular organisms. In this study, we analyzed the role of the Caenorhabditis elegans Drs2p homologue transbilayer amphipath transporter (TAT)-1 in intracellular trafficking. tat-1 is expressed in many tissues including the intestine, the epidermis and the nervous system. In intestinal cells, tat-1 loss-of-function mutants accumulate large vacuoles of mixed endolysosomal identity positive for the lysosomal protein LMP-1. In addition, they lack the same class of storage granules as lmp-1 mutants, suggesting that part of the tat-1 phenotype might result from LMP-1 sequestration in an aberrant compartment. Epidermal cells mutant for tat-1 contain acidified giant hybrid multivesicular bodies probably corresponding to endolysosomal intermediate compartments or deficient lysosomes. Finally, TAT-1 is required for yolk uptake in oocytes and an early step of fluid-phase endocytosis in the intestine. Hence, TAT-1 is required at multiple steps of the endolysosomal pathway, at least in part by ensuring proper trafficking of cell-specific effector proteins. |
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Keywords: | aminophospholipid translocase C elegans endosome MVB TAT-1 |
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