Basis of lethality in C. elegans lacking CUP-5, the Mucolipidosis Type IV orthologue

Developmental Biology
Lara SchaheenHanna Fares

Abstract

Mutations in MCOLN1, which encodes the protein h-mucolipin-1, result in the lysosomal storage disease Mucolipidosis Type IV. Studies on CUP-5, the human orthologue of h-mucolipin-1 in Caenorhabditis elegans, have shown that these proteins are required for lysosome biogenesis. We show here that the lethality in cup-5 mutant worms is due to two defects, starvation of embryonic cells and general developmental defects. Starvation leads to apoptosis through a CED-3-mediated pathway. We also show that providing worms with a lipid-soluble metabolite partially rescues the embryonic lethality but has no effect on the developmental defects, the major cause of the lethality. These results indicate that supplementing the metabolic deficiency of Mucolipidosis Type IV patients mat not be sufficient to alleviate the symptoms due to tissue degeneration.

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Citations

Apr 30, 2014·WormBook : the Online Review of C. Elegans Biology·Ken SatoBarth D Grant
Dec 25, 2007·BMC Cell Biology·Eric G ThompsonHanna Fares
May 28, 2008·The Journal of Experimental Medicine·Mark T MiedelKirill Kiselyov
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Oct 23, 2008·Traffic·Anne-Françoise RuaudSimon Tuck
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Dec 2, 2010·Biochemical Society Transactions·Gideon BachAviram Kogot-Levin
Jan 27, 2017·G3 : Genes - Genomes - Genetics·Kevin GeeHanna Fares
Dec 12, 2018·Nature Methods·Nagarjun NarayanaswamyYamuna Krishnan

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