title: Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog.
abstract: Loss of the human mucolipin-1 gene underlies mucolipidosis type IV (MLIV), a lysosomal storage disease that results in severe developmental neuropathology. Unlike other lysosomal storage diseases, MLIV is not associated with a lack of lysosomal hydrolases; instead, MLIV cells display abnormal endocytosis of lipids and accumulate large vesicles, indicating that a defect in endocytosis may underlie the disease. Here we report the identification of a loss-of-function mutation in the Caenorhabditis elegans mucolipin-1 homolog, cup-5, and show that this mutation results in an enhanced rate of uptake of fluid-phase markers, decreased degradation of endocytosed protein and accumulation of large vacuoles. Overexpression of cup-5(+) causes the opposite phenotype, indicating that cup-5 activity controls aspects of endocytosis. Studies in model organisms such as C. elegans have helped illuminate fundamental mechanisms involved in normal cellular function and human disease; thus the C. elegans cup-5 mutant may be a useful model for studying conserved aspects of mucolipin-1 structure and function and for assessing the effects of potential therapeutic compounds.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York, USA. fares@email.arizona.edu
authors.forename: H
authors.initials: H
authors.lastname: Fares
authors.forename: I
authors.initials: I
authors.lastname: Greenwald
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D004705:Endocytosis / Q000235:genetics*; D015801:Helminth Proteins / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009081:Mucolipidoses / Q000209:etiology / Q000235:genetics; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels
chemical_list: C426649:CUP-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; C416674:MCOLN1 protein, human; D008565:Membrane Proteins; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels