title: Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway.
abstract: Mucolipin-1 (MLN1) is a membrane protein with homology to the transient receptor potential channels and other non-selective cation channels. It is encoded by the MCOLN1 gene, which is mutated in patients with mucolipidosis type IV (MLIV), an autosomal recessive disease that is characterized by severe abnormalities in neurological development as well as by ophthalmologic defects. At the cellular level, MLIV is associated with abnormal lysosomal sorting and trafficking. Here we identify the channel function of human MLN1 and characterize its properties. MLN1 represents a novel Ca(2+)-permeable channel that is transiently modulated by changes in [Ca(2+)]. It is also permeable to Na(+) and K(+). Large unitary conductances were measured in the presence of these cations. With its Ca(2+) permeability and modulation by [Ca(2+)], MLN1 could play a major role in Ca(2+) transport regulating lysosomal exocytosis and potentially other phenomena related to the trafficking of late endosomes and lysosomes.
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Janice M
authors.initials: JM
authors.lastname: LaPlante
authors.forename: John
authors.initials: J
authors.lastname: Falardeau
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: Marie
authors.initials: M
authors.lastname: Kanazirska
authors.forename: Edward M
authors.initials: EM
authors.lastname: Brown
authors.forename: Susan A
authors.initials: SA
authors.lastname: Slaugenhaupt
authors.forename: Peter M
authors.initials: PM
authors.lastname: Vassilev
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane; D004553:Electric Conductivity; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D017136:Ion Transport; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009081:Mucolipidoses / Q000235:genetics; D009865:Oocytes; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; D014981:Xenopus
chemical_list: D002412:Cations; D007473:Ion Channels; D007476:Ionophores; C416674:MCOLN1 protein, human; D008565:Membrane Proteins; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; D015759:Ionomycin; D002118:Calcium