title: Mucolipin-1 is a lysosomal membrane protein required for intracellular lactosylceramide traffic.
abstract: Mucolipin-1 is a membrane protein encoded by the gene MCOLN1, mutations in which result in the lysosomal storage disorder mucolipidosis type IV (MLIV). Efficient lysosomal targeting of mucolipin-1 requires di-leucine motifs in both the N-terminal and the C-terminal cytosolic tails. We have shown that aberrant lactosylceramide trafficking in MLIV cells may be rescued by wild-type mucolipin-1 expression but not by mucolipin-1 mistargeted to the plasma membrane or by lysosome-localized mucolipin-1 mutated in its predicted ion pore-selectivity region. Our data demonstrate that the correct localization of mucolipin-1 and the integrity of its ion pore are essential for its physiological function in the late endocytic pathway.
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Pryor
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
authors.forename: J Paul
authors.initials: JP
authors.lastname: Luzio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D007790:Lactosylceramides / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009081:Mucolipidoses / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D051381:Rats; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D050051:Transient Receptor Potential Channels
chemical_list: D015703:Antigens, CD; D007790:Lactosylceramides; C416674:MCOLN1 protein, human; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; C009744:CDw17 antigen; D002784:Cholesterol; D007930:Leucine