Overexpression of wild-type and mutant mucolipin proteins in mammalian cells: effects on the late endocytic compartment organization

FEBS Lett. 2004 Jun 4;567(2-3):219-24. doi: 10.1016/j.febslet.2004.04.080.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Biomarkers
  • COS Cells
  • Cell Compartmentation / physiology*
  • Chlorocebus aethiops
  • Endocytosis / physiology*
  • Gene Expression
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Models, Molecular
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Subcellular Fractions / metabolism
  • TRPM Cation Channels
  • Transfection
  • Transient Receptor Potential Channels

Substances

  • Biomarkers
  • MCOLN1 protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • Recombinant Proteins
  • TRPM Cation Channels
  • Transient Receptor Potential Channels