Medical Research Council Laboratory of Molecular Biology, Cambridge, England, UK.
Medical Research Council Laboratory of Molecular Biology, Cambridge, England, UK
J Cell Biol. 2018 Feb 5;217(2):601-617. doi: 10.1083/jcb.201705068. Epub 2017 Dec 22.
Originally identified in yeast, transport protein particle (TRAPP) complexes are Rab GTPase exchange factors that share a core set of subunits. TRAPPs were initially found to act on Ypt1, the yeast orthologue of Rab1, but recent studies have found that yeast TRAPPII can also activate the Rab11 orthologues Ypt31/32. Mammals have two TRAPP complexes, but their role is less clear, and they contain subunits that are not found in the yeast complexes but are essential for cell growth. To investigate TRAPP function in metazoans, we show that have two TRAPP complexes similar to those in mammals and that both activate Rab1, whereas one, TRAPPII, also activates Rab11. TRAPPII is not essential but becomes so in the absence of the gene that encodes the orthologue of the SH3BP5 family of Rab11 guanine nucleotide exchange factors (GEFs). Thus, in metazoans, Rab1 activation requires TRAPP subunits not found in yeast, and Rab11 activation is shared by TRAPPII and an unrelated GEF that is metazoan specific.
最初在酵母中鉴定出的转运蛋白颗粒(TRAPP)复合物是 Rab GTPase 交换因子,它们共享一组核心亚基。TRAPP 最初被发现作用于 Ypt1,即 Rab1 的酵母同源物,但最近的研究发现,酵母 TRAPPII 也可以激活 Rab11 的同源物 Ypt31/32。哺乳动物有两种 TRAPP 复合物,但它们的作用不太清楚,而且它们包含在酵母复合物中没有发现的亚基,但这些亚基对细胞生长是必不可少的。为了研究 TRAPP 在后生动物中的功能,我们表明 有两种类似于哺乳动物的 TRAPP 复合物,两者都能激活 Rab1,而一种称为 TRAPPII 的复合物也能激活 Rab11。TRAPPII 不是必需的,但在缺乏编码 SH3BP5 家族 Rab11 鸟嘌呤核苷酸交换因子(GEF)的 基因时,它就变得必需了。因此,在后生动物中,Rab1 的激活需要在酵母中未发现的 TRAPP 亚基,而 Rab11 的激活则由 TRAPPII 和一种与 TRAPPII 无关的、专门在后生动物中存在的 GEF 共同完成。