当前位置:生物帮 > 国内研究 > 基因&基因组 > 正文

EMBO Journal:香港中文大学余小彬教授发表脂代谢研究成果

相关专题:
摘要 : 2016年12月21日,国际知名学术期刊《EMBO Reports》杂志上在线发表了深圳大学医学部基础医学院解剖组胚与发育生物学系李春满助理教授与香港中文大学余小彬教授团队题为《COPI-TRAPPII活化Rab18并调节其与脂滴关系》(COPI-TRAPPII activates Rab18 and regulates its lipid droplet association)的研究论文。

2016年12月21日,国际知名学术期刊《EMBO Reports》杂志上在线发表了深圳大学医学部基础医学院解剖组胚与发育生物学系李春满助理教授与香港中文大学余小彬教授团队题为《COPI-TRAPPII活化Rab18并调节其与脂滴关系》(COPI-TRAPPII activates Rab18 and regulates its lipid droplet association)的研究论文。李春满助理教授是本文唯一第一作者,余小彬教授为通讯作者。

脂代谢紊乱是引起肥胖,脂肪肝,糖尿病与动脉粥样硬化的重要危险因素。细胞内的脂滴(Lipid droplet)作为中性脂肪的贮存结构,与脂代谢平衡密切相关。已有研究表明,活化的GTP形式的小G蛋白Rab18会附着在脂滴表面,促进脂滴与内质网的结合,从而参与甘油三酯的分解代谢。而决定Rab18转化为GTP形式并结合在脂滴表面的鸟苷酸活化因子(GEF)一直没有被发现。该文章首次报道,转运蛋白复合体II(TRAPPII)是Rab18的GEF。当细胞内敲除TRAPPII后,Rab18不再附着于脂滴表面,脂肪分解代谢受到抑制,细胞内出现大量脂滴聚集。进一步的研究表明,在脂肪分解代谢中发挥重要调节作用COPI复合体,是调控TRAPPII参与脂代谢的重要分子。这些结果首次发现了细胞内参与脂肪分解代谢的COPI-TRAPPII-Rab18信号通路的存在,有助于进一步揭示脂肪肝,糖尿病等代谢性疾病的发病机理。

原文链接:

COPI–TRAPPII activates Rab18 and regulates its lipid droplet association

原文摘要:

The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1. Inactivation of TRAPPII‐specific subunits by various methods including sirna depletion and CRISPR–Cas9‐mediated deletion reduced lipolysis and resulted in aberrantly large lipid droplets. Recruitment of Rab18 onto lipid droplet (LD) surface was defective in TRAPPII‐deleted cells, but the localization of Rab1 on Golgi was not affected. COPI regulates LD homeostasis. We found that the previously documented interaction between TRAPPII and COPI was also required for the recruitment of Rab18 to the LD. We hypothesize that the interaction between COPI and TRAPPII helps bring TRAPPII onto LD surface, and TRAPPII, in turn, activates Rab18 and recruits it on the LD surface to facilitate its functions in LD homeostasis.

DOI 10.15252/embj.201694866

作者:余小彬 点击:

    热门文章TOP