Mahuran D J
Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ont. M5G 1X8, Canada.
Biochim Biophys Acta. 1998 Jul 31;1393(1):1-18. doi: 10.1016/s0005-2760(98)00057-5.
Although there is only one documented function carried out by the GM2 activator protein in the lysosome, new information suggests that other less obvious roles may also be played by this protein in vivo. This information includes data demonstrating that the GM2 activator is a secretory, as well as a lysosomal protein, and that cells possess a carbohydrate-independent mechanism to re-capture the activator, with or without bound lipid, from the extracellular fluid. Additionally the GM2 activator has been shown to bind, solubilize and transport a broad spectrum of lipid molecules, such as glycolipids, gangliosides and at least one phosphoacylglycerol, between liposomes. At pH 7 the GM2 activator's rate of lipid transport is reduced by only 50% from its maximum rate which is achieved at approx. pH 5, suggesting that the GM2 activator may serve as a general intra- and/or inter-cellular lipid transport protein in vivo. Since the late 1970s the lysosomal form of the GM2 activator has been known to act as a substrate-specific co-factor for the hydrolysis of GM2 ganglioside by beta-hexosaminidase A. Gangliosides are a class of negatively charged glycolipids particularly abundant in neuronal cells which have been linked to numerous in vivo functions, such as memory formation and signal transduction events. Deficiency of the GM2 activator protein results in the storage of GM2 ganglioside and severe neurological disease, the AB-variant form of GM2 gangliosidosis, usually culminating in death before the age of 4 years. The exact mode-of-action of the GM2 activator in its role as a co-factor, and its specificity for various glycolipids are currently matters of debate in the literature.
尽管在溶酶体中已记录的GM2激活蛋白执行的功能只有一种，但新信息表明该蛋白在体内可能还发挥着其他不太明显的作用。这些信息包括数据表明GM2激活蛋白不仅是一种溶酶体蛋白，还是一种分泌蛋白，并且细胞拥有一种不依赖碳水化合物的机制，可从细胞外液中重新捕获结合或未结合脂质的激活蛋白。此外，GM2激活蛋白已被证明能在脂质体之间结合、溶解并转运多种脂质分子，如糖脂、神经节苷脂和至少一种磷酸酰甘油。在pH 7时，GM2激活蛋白的脂质转运速率仅比其在约pH 5时达到的最大速率降低50%，这表明GM2激活蛋白在体内可能作为一种通用的细胞内和/或细胞间脂质转运蛋白。自20世纪70年代末以来，人们就知道GM2激活蛋白的溶酶体形式可作为β-己糖胺酶A水解GM2神经节苷脂的底物特异性辅因子。神经节苷脂是一类带负电荷的糖脂，在神经元细胞中特别丰富，与许多体内功能有关，如记忆形成和信号转导事件。GM2激活蛋白的缺乏会导致GM2神经节苷脂的蓄积和严重的神经疾病，即GM2神经节苷脂贮积症的AB变异型，通常在4岁前死亡。GM2激活蛋白作为辅因子的具体作用方式及其对各种糖脂的特异性目前在文献中仍存在争议。
