Loss of the human mucolipin-1 gene underlies mucolipidosis type IV (MLIV), a lysosomal storage disease that results in severe developmental neuropathology. Unlike other lysosomal storage diseases, MLIV is not associated with a lack of lysosomal hydrolases; instead, MLIV cells display abnormal endocytosis of lipids and accumulate large vesicles, indicating that a defect in endocytosis may underlie the disease. 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-5(+) 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.

中文翻译：

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秀丽隐杆线虫黏液素1同源物CUP-5对内吞作用的调节。

人类粘液素-1基因的缺失是粘液脂缺乏症IV型（MLIV）的基础，粘液脂病是一种溶酶体贮积病，可导致严重的发育性神经病理学。与其他溶酶体贮积病不同，MLIV与缺乏溶酶体水解酶无关。相反，MLIV细胞表现出异常的脂质内吞作用并积聚大囊泡，表明内吞作用缺陷可能是该疾病的基础。在这里，我们报告的秀丽隐杆线虫黏液素1同源物，cup-5，功能丧失突变的鉴定，并表明该突变导致液相标记的摄取率提高，内吞蛋白降解降低和大液泡的积累。cup-5（+）的过表达导致相反的表型，表明cup-5活性控制着内吞作用。对秀丽隐杆线虫等模型生物的研究有助于阐明正常细胞功能和人类疾病的基本机制。因此，秀丽隐杆线虫cup-5突变体可能是有用的模型，可用于研究粘蛋白-1结构和功能的保守方面以及评估潜在治疗化合物的作用。