生物
胰岛素抵抗
发病机制
基因亚型
神经节苷脂
免疫系统
亚细胞定位
脂质微区
炎症
细胞生物学
细胞质
免疫学
胰岛素
遗传学
内分泌学
基因
膜
作者
Jin-ichi Inokuchi,Kei-ichiro Inamori,Kazuya Kabayama,Masakazu Nagafuku,Satoshi Uemura,Shinji Go,Akemi Suzuki,Isao Ohno,Hirotaka Kanoh,Fumi Shishido
出处
期刊:Progress in Molecular Biology and Translational Science
日期:2018-01-01
卷期号:: 151-195
被引量:46
标识
DOI:10.1016/bs.pmbts.2017.10.004
摘要
Since the successful molecular cloning in 1998 of GM3 synthase (GM3S, ST3GAL5), the enzyme responsible for initiating biosynthesis of all complex gangliosides, the efforts of our research group have been focused on clarifying the physiological and pathological implications of gangliosides, particularly GM3. We have identified isoforms of GM3S proteins having distinctive lengths of N-terminal cytoplasmic tails, and found that these cytoplasmic tails define subcellular localization, stability, and in vivo activity of GM3S isoforms. Our studies of the molecular pathogenesis of type 2 diabetes, focused on interaction between insulin receptor and GM3 in membrane microdomains, led to a novel concept: type 2 diabetes and certain other lifestyle-related diseases are membrane microdomain disorders resulting from aberrant expression of gangliosides. This concept has enhanced our understanding of the pathophysiological roles of GM3 and related gangliosides in various diseases involving chronic inflammation, such as insulin resistance, leptin resistance, and T-cell function and immune disorders (e.g., allergic asthma). We also demonstrated an essential role of GM3 in murine and human auditory systems; a common pathological feature of GM3S deficiency is deafness. This is the first direct link reported between gangliosides and auditory functions.
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