Lysosomal exocytosis is impaired in mucolipidosis type IV
Lysosomal exocytosis is impaired in mucolipidosis type IV
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DOI：
10.1016/j.ymgme.2006.05.016
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发表时间：
2006-12-01
影响因子：
3.8
通讯作者：
Vassilev, Peter M.
中科院分区：
文献类型：
--
作者：
LaPlante, Janice M.;Sun, Mei;Vassilev, Peter M.
IV型黏脂沉积症(MLIV)是一种常染色体隐性遗传病，以严重的神经功能障碍、神经功能缺陷和胃功能障碍为特征。MLIV细胞在晚期内小体/溶酶体(LEL)途径中存在缺陷，导致溶酶体内含物积聚。利用非洲爪哇卵母细胞表达系统，我们先前证明了由MCOLN1基因编码的粘蛋白-1(MLN1)是一种非选择性的钙离子通道，它受细胞内钙离子升高的瞬时调节。我们进一步证明，MLN1在溶酶体胞吐过程中被转移到质膜上。在这项研究中，我们发现MLIV患者成纤维细胞的溶酶体胞吐功能受损，表明MLN1在这一过程中发挥着积极的作用。此外，我们还表明，野生型MLN1基因可以挽救胞吐作用，这表明基于这一重要细胞功能恢复的治疗是可能的。(C)2006 Elsevier Inc.保留所有权利。
Mucolipidosis type IV (MLIV) is an autosomal recessive disease characterized by severe neurological impairment, oplithalmologic defects, and gastric dysfunction. MLIV cells have a deficiency in the late endosomal/lysosomal (LEL) pathway that results in the buildup of lysosomal inclusions. Using a Xenopus oocyte expression system, we previously showed that mucolipin-1 (MLN1), the protein encoded by the MCOLN1 gene is a Ca2+-permeable non-selective cation channel that is transiently modulated by elevations in intracellular Ca2+. We further showed that MLN1 is translocated to the plasma membrane during lysosomal exocytosis. In this study we show that lysosomal exocytosis is impaired in fibroblasts from MLIV patients, indicating that MLN1 plays an active role in this process. Further, we show that transfection with wild type MLN1 cDNA rescues exocytosis, suggesting the possibility of treatments based on the restoration of this crucial cellular function. (c) 2006 Elsevier Inc. All rights reserved.