Schaheen Lara, Dang Hope, Fares Hanna
Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA.
Dev Biol. 2006 May 15;293(2):382-91. doi: 10.1016/j.ydbio.2006.02.008.
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.
编码蛋白质h-粘脂素-1的MCOLN1发生突变会导致溶酶体贮积病IV型粘脂沉积症。对秀丽隐杆线虫中h-粘脂素-1的人类同源物CUP-5的研究表明，这些蛋白质是溶酶体生物发生所必需的。我们在此表明，cup-5突变体蠕虫的致死性归因于两个缺陷，即胚胎细胞饥饿和一般发育缺陷。饥饿通过CED-3介导的途径导致细胞凋亡。我们还表明，为蠕虫提供一种脂溶性代谢物可部分挽救胚胎致死性，但对发育缺陷（致死性的主要原因）没有影响。这些结果表明，补充IV型粘脂沉积症患者的代谢缺陷可能不足以缓解由于组织退化引起的症状。
