title: Caenorhabditis elegans numb inhibits endocytic recycling by binding TAT-1 aminophospholipid translocase.
abstract: Numb regulates endocytosis in many metazoans, but the mechanism by which it functions is not completely understood. Here we report that the Caenorhabditis elegans Numb ortholog, NUM-1A, a regulator of endocytic recycling, binds the C isoform of transbilayer amphipath transporter-1 (TAT-1), a P4 family adenosine triphosphatase and putative aminophospholipid translocase that is required for proper endocytic trafficking. We demonstrate that TAT-1 is differentially spliced during development and that TAT-1C-specific splicing occurs in the intestine where NUM-1A is known to function. NUM-1A and TAT-1C colocalize in vivo. We have mapped the binding site to an NXXF motif in TAT-1C. This motif is not required for TAT-1C function but is required for NUM-1A's ability to inhibit recycling. We demonstrate that num-1A and tat-1 defects are both suppressed by the loss of the activity of PSSY-1, a phosphatidylserine (PS) synthase. PS is mislocalized in intestinal cells with defects in tat-1 or num-1A function. We propose that NUM-1A inhibits recycling by inhibiting TAT-1C's ability to translocate PS across the membranes of recycling endosomes.
authors.affiliation: Umeå Center for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Nilsson
authors.forename: Eva
authors.initials: E
authors.lastname: Jonsson
authors.forename: Simon
authors.initials: S
authors.lastname: Tuck
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D021381:Protein Transport
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D026901:Membrane Transport Proteins; D049294:Phospholipid Transfer Proteins; D020033:Protein Isoforms; C425313:num-1 protein, C elegans; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase; D000251:Adenosine Triphosphatases; C522446:TAT-1 protein, C elegans