title: The plasma membrane calcium ATPase MCA-3 is required for clathrin-mediated endocytosis in scavenger cells of Caenorhabditis elegans.
abstract: Plasma membrane Ca2+ ATPases (PMCAs) maintain proper intracellular Ca2+ levels by extruding Ca2+ from the cytosol. PMCA genes and splice forms are expressed in tissue-specific patterns in vertebrates, suggesting that these isoforms may regulate specific biological processes. However, knockout mutants die as embryos or undergo cell death; thus, it is unclear whether other cell processes utilize PMCAs or whether these pumps are largely committed to the control of toxic levels of calcium. Here, we analyze the role of the PMCA gene, mca-3, in Caenorhabditis elegans. We report that partial loss-of-function mutations disrupt clathrin-mediated endocytosis in a class of scavenger cells called coelomocytes. Moreover, components of early endocytic machinery are mislocalized in mca-3 mutants, including phosphatidylinositol-4,5-bisphosphate, clathrin and the Eps15 homology (EH) domain protein RME-1. This defect in endocytosis in the coelomocytes can be reversed by lowering calcium. Together, these data support a function for PMCAs in the regulation of endocytosis in the C. elegans coelomocytes. In addition, they suggest that endocytosis can be blocked by high calcium levels.
authors.affiliation: Department of Biology and Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Bednarek
authors.forename: Lara
authors.initials: L
authors.lastname: Schaheen
authors.forename: Jayne
authors.initials: J
authors.lastname: Gaubatz
authors.forename: Erik M
authors.initials: EM
authors.lastname: Jorgensen
authors.forename: Hanna
authors.initials: H
authors.lastname: Fares
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000172:deficiency / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D033922:Clathrin Heavy Chains / Q000235:genetics / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism / Q000502:physiology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D022821:RNA Splice Sites / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; D002966:Clathrin; D007295:Inositol Phosphates; D020033:Protein Isoforms; C486205:RME-1 protein, C elegans; D022821:RNA Splice Sites; D011993:Recombinant Fusion Proteins; D033922:Clathrin Heavy Chains; D049452:Green Fluorescent Proteins; D004533:Egtazic Acid; C091533:glycerophosphoinositol 4,5-bisphosphate; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium