TY - JOUR
T1 - Basis of lethality in C. elegans lacking CUP-5, the Mucolipidosis Type IV orthologue.
AU - Schaheen, Lara
AU - Dang, Hope
AU - Fares, Hanna
N1 - Funding Information:
We are grateful for Barth Grant, Peg MacMorris, Stuart Kim, and James McGhee for antibodies to RME-2, YP170, LIN-12, and IFB-2, respectively. We also thank Alicia Melendez for the GFP∷LGG-1 construct and the C. elegans Gene Knockout Consortium for the deletion alleles of tag-283. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources. The authors declare that they have no competing financial interests. This work was funded by a March of Dimes grant (#6-FY04-60) to H.F.
PY - 2006/5/15
Y1 - 2006/5/15
N2 - 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.
AB - 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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U2 - 10.1016/j.ydbio.2006.02.008
DO - 10.1016/j.ydbio.2006.02.008
M3 - Article
C2 - 16530747
AN - SCOPUS:33745685199
SN - 0012-1606
VL - 293
SP - 382
EP - 391
JO - Developmental biology
JF - Developmental biology
IS - 2
ER -