title: C. elegans Disabled is required for cell-type specific endocytosis and is essential in animals lacking the AP-3 adaptor complex.
abstract: Disabled proteins are a conserved family of monomeric adaptor proteins that in mammals are implicated in the endocytosis of lipoprotein receptors. Previous studies have shown that the sole Caenorhabditis elegans Disabled homologue, DAB-1, is involved in the lipoprotein receptor-mediated secretion of a fibroblast growth factor. We show here that DAB-1 is essential for the uptake of yolk protein by developing oocytes, and for the localisation of the yolk receptor RME-2. The localisation of DAB-1 in oocytes is itself dependent upon clathrin and AP2, consistent with DAB-1 acting as a clathrin-associated sorting protein during yolk protein endocytosis. DAB-1 is also required for the endocytosis of molecules from the pseudocoelomic fluid by the macrophage-like coelomocytes, and is broadly expressed in epithelial tissues, consistent with a general role in receptor-mediated endocytosis. We also show that dab-1 mutations are synthetic lethal in combination with loss-of-function mutations affecting the AP-1 and AP-3 complexes, suggesting that the reduced fluid and membrane uptake exhibited by dab-1 mutants sensitises them to defects in other trafficking pathways.
authors.affiliation: Cell and Developmental Biology Program, School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Holmes
authors.forename: Aileen
authors.initials: A
authors.lastname: Flett
authors.forename: Damien
authors.initials: D
authors.lastname: Coudreuse
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Korswagen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pettitt
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D004527:Egg Proteins / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D011973:Receptors, LDL / Q000302:isolation & purification / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D029742:Caenorhabditis elegans Proteins; D002966:Clathrin; C510381:DAB-1 protein, C elegans; D004527:Egg Proteins; D050505:Mutant Proteins; C514538:RME-2 protein, C elegans; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins