Inefficient processing of an olfactomedin-deficient myocilin mutant:: Potential physiological relevance to glaucoma
Inefficient processing of an olfactomedin-deficient myocilin mutant:: Potential physiological relevance to glaucoma
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DOI：
10.1006/bbrc.2001.4624
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发表时间：
2001-04-06
影响因子：
3.1
通讯作者：
Borrás, T
中科院分区：
文献类型：
--
作者：
Caballero, M;Borrás, T
TIGR/MYOC（肌球蛋白）（一种功能未知的分泌蛋白）的突变最近被认为与青光眼有关。大多数已知的突变映射到C-末端，嗅觉调节素样结构域。我们以前已经表明，与野生型相反，截短形式的myocilin缺乏嗅介蛋白结构域不分泌。在这项研究中，我们提出的证据表明，突变蛋白质是不正确的加工内质网（ER）和积累成不溶性的聚集体。此外，我们表明，存在的突变体蛋白质的数量增加诱导一部分的可溶性，天然myocilin移动到不溶性部分。鉴于这种蛋白质聚集体在几种衰老相关疾病的病因学中的重要性，我们提出嗅觉调节素缺陷突变体可能通过涉及错误折叠蛋白质的细胞内积累的机制而导致青光眼的病理学。(C)北京：科学出版社.
Mutations in TIGR/MYOC (myocilin), a secretory protein of unknown function, have been recently linked to glaucoma. Most known mutations map to the C-terminus, an olfactomedin-like domain. We have previously shown that, in contrast to the wild-type, a truncated form of myocilin lacking the olfactomedin domain is not secreted. In this study, we present evidence that the mutant protein is not correctly processed in the endoplasmic reticulum (ER) and accumulates into insoluble aggregates. In addition, we show that the presence of increasing amounts of mutant protein induces a fraction of the soluble, native myocilin to move to the insoluble fraction. Given the importance of such protein aggregates in the etiology of several aging-related diseases, we propose that olfactomedin-defective mutants might contribute to the pathology of glaucoma through a mechanism involving intracellular accumulation of misfolded proteins. (C) 2001 Academic Press.