title: Overexpression of wild-type and mutant mucolipin proteins in mammalian cells: effects on the late endocytic compartment organization.
abstract: Mucolipin-1 is a 65-kDa membrane protein encoded by the MCOLN1 gene, which is mutated in patients with mucolipidosis type IV (MLIV), a rare neurodegenerative lysosomal storage disorder. We studied the subcellular localization of wild-type and three different mutant forms (T232P, F408del and F465L) of mucolipin by expressing Myc-tagged proteins in HeLa cells. The overexpressed wild-type mucolipin colocalizes to late endocytic structures and induces an aberrant distribution of these compartments. F408del and F465L MLIV mutant proteins show a distribution similar to the wild-type protein, whereas T232P is retained in the endoplasmic reticulum. Among the mutants, only F408del induces a redistribution of the late endocytic compartment. These findings suggest that the overexpression of the mucolipin cation channel influences the dynamic equilibrium of late endocytic compartments.
authors.affiliation: Sezione di Biologia e Genetica, Dipartimento di Scienze Biomediche e Biotecnologie, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Manzoni
authors.forename: E
authors.initials: E
authors.lastname: Monti
authors.forename: R
authors.initials: R
authors.lastname: Bresciani
authors.forename: A
authors.initials: A
authors.lastname: Bozzato
authors.forename: S
authors.initials: S
authors.lastname: Barlati
authors.forename: M T
authors.initials: MT
authors.lastname: Bassi
authors.forename: G
authors.initials: G
authors.lastname: Borsani
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D015415:Biomarkers; D019556:COS Cells; D002451:Cell Compartmentation / Q000502:physiology*; D002522:Chlorocebus aethiops; D004705:Endocytosis / Q000502:physiology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018613:Microscopy, Confocal; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D050053:TRPM Cation Channels; D014162:Transfection; D050051:Transient Receptor Potential Channels
chemical_list: D015415:Biomarkers; C416674:MCOLN1 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels