糖基化获得：髓鞘蛋白零突变的新病理机制。
Gain of glycosylation: a new pathomechanism of myelin protein zero mutations.
机构信息
Department of Neurosciences, Ophthalmology, and Genetics, University of Genoa, Genoa, Italy.
出版信息
Ann Neurol. 2012 Mar;71(3):427-31. doi: 10.1002/ana.22695.
Abstract
We report the first case of a missense mutation in MPZ causing a gain of glycosylation in myelin protein zero, the main protein of peripheral nervous system myelin. The patient was affected by a severe demyelinating neuropathy caused by a missense mutation, D32N, that created a new glycosylation sequence. We confirmed that the mutant protein is hyperglycosylated, is partially retained into the Golgi apparatus in vitro, and disrupts intercellular adhesion. By sequential experiments, we demonstrated that hyperglycosylation is the main mechanism of this mutation. Gain of glycosylation is a new mechanism in Charcot-Marie-Tooth type 1B.
摘要
我们报告了首例 MPZ 错义突变导致髓鞘蛋白零（周围神经系统髓鞘的主要蛋白）糖基化增加的病例。该患者患有严重的脱髓鞘神经病，由错义突变 D32N 引起，该突变产生了新的糖基化序列。我们证实突变蛋白发生高糖基化，体外部分滞留在高尔基体中，并破坏细胞间黏附。通过连续的实验，我们证明了高糖基化是该突变的主要机制。获得糖基化是 Charcot-Marie-Tooth 型 1B 的一种新机制。
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Science. 2010 Jun 11;328(5984):1415-8. doi: 10.1126/science.1187735. Epub 2010 May 6.
2
Aberrant trafficking of human melanocortin 1 receptor variants associated with red hair and skin cancer: Steady-state retention of mutant forms in the proximal golgi.与红发和皮肤癌相关的人类促黑素皮质素1受体变体的异常转运：突变形式在高尔基体近端的稳态滞留。
J Cell Physiol. 2009 Sep;220(3):640-54. doi: 10.1002/jcp.21804.
3
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Mol Biol Cell. 2004 Oct;15(10):4556-67. doi: 10.1091/mbc.e04-06-0480. Epub 2004 Aug 10.
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