GM2激活蛋白,其作为GM2水解的辅助因子和一般糖脂转运蛋白的作用

Don J Mahuran
{"title":"GM2激活蛋白,其作为GM2水解的辅助因子和一般糖脂转运蛋白的作用","authors":"Don J Mahuran","doi":"10.1016/S0005-2760(98)00057-5","DOIUrl":null,"url":null,"abstract":"<div><p>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 β-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.</p></div>","PeriodicalId":100162,"journal":{"name":"Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1998-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0005-2760(98)00057-5","citationCount":"69","resultStr":"{\"title\":\"The GM2 activator protein, its roles as a co-factor in GM2 hydrolysis and as a general glycolipid transport protein\",\"authors\":\"Don J Mahuran\",\"doi\":\"10.1016/S0005-2760(98)00057-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 β-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.</p></div>\",\"PeriodicalId\":100162,\"journal\":{\"name\":\"Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1998-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/S0005-2760(98)00057-5\",\"citationCount\":\"69\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0005276098000575\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0005276098000575","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 69

摘要

虽然GM2激活蛋白在溶酶体中只有一种被记录的功能,但新的信息表明,该蛋白在体内也可能发挥其他不太明显的作用。这些信息包括数据表明GM2激活剂是一种分泌性蛋白,也是一种溶酶体蛋白,并且细胞具有不依赖碳水化合物的机制,无论是否结合脂质,都可以从细胞外液中重新捕获激活剂。此外,GM2激活剂已被证明在脂质体之间结合、溶解和运输广泛的脂质分子,如糖脂、神经节苷和至少一种磷酸酰甘油。在pH值为7时,GM2激活剂的脂质转运率仅比其最大转运率降低了50%。pH值为5,表明GM2激活剂可能在体内作为一般的细胞内和/或细胞间脂质转运蛋白。自20世纪70年代末以来,GM2激活剂的溶酶体形式已被认为是β-己糖氨酸酶a水解GM2神经节苷脂的底物特异性辅助因子。神经节苷脂是一类带负电荷的糖脂类,在神经元细胞中尤其丰富,与许多体内功能有关,如记忆形成和信号转导事件。GM2激活蛋白的缺乏导致GM2神经节苷脂的储存和严重的神经系统疾病,即GM2神经节苷脂病的ab变异形式,通常在4岁前死亡。GM2激活剂作为辅助因子的确切作用方式及其对各种糖脂的特异性目前在文献中存在争议。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
The GM2 activator protein, its roles as a co-factor in GM2 hydrolysis and as a general glycolipid transport protein

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 β-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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein Cholesterol synthesis is increased in mixed hyperlipidaemia The level of 7-dehydrocholesterol in plasma reflects the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the human liver Fatty acid α-oxidation of tetradecylthioacetic acid and tetradecylthiopropionic acid in cucumber (Cucumis sativus) Inductive electron-withdrawal from ammonium ion headgroups of cationic lipids and the influence on DNA transfection
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1