Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog

Hanna F Fares, Iva Greenwald

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Loss of the human mucolipin-1 gene underlies mucolipidosis type IV (MLIV), a lysosomal storage disease that results in severe developmental neuropathology1-3. Unlike other lysosomal storage diseases, MLIV is not associated with a lack of lysosomal hydrolases4; instead, MLIV cells display abnormal endocytosis of lipids and accumulate large vesicles, indicating that a defect in endocytosis may underlie the disease4-6. 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-S(+) 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.

Original languageEnglish (US)
Pages (from-to)64-68
Number of pages5
JournalNature Genetics
Volume28
Issue number1
DOIs
StatePublished - 2001

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Caenorhabditis elegans
Mucolipidoses
Endocytosis
Lysosomal Storage Diseases
Mutation
Therapeutic Uses
Vacuoles
Proteolysis
Phenotype
Lipids
Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Regulation of endocytosis by CUP-5, the Caenorhabditis elegans mucolipin-1 homolog. / Fares, Hanna F; Greenwald, Iva.

In: Nature Genetics, Vol. 28, No. 1, 2001, p. 64-68.

Research output: Contribution to journalArticle

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