Thomas Laura L, Highland Carolyn M, Fromme J Christopher
Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853.
Mol Biol Cell. 2021 May 15;32(11):1104-1120. doi: 10.1091/mbc.E20-10-0664. Epub 2021 Mar 31.
Rab family GTPases are key organizers of membrane trafficking and function as markers of organelle identity. Accordingly, Rab GTPases often occupy specific membrane domains, and mechanisms exist to prevent the inappropriate mixing of distinct Rab domains. The yeast Golgi complex can be divided into two broad Rab domains: Ypt1 (Rab1) and Ypt6 (Rab6) are present at the early/medial Golgi and sharply transition to Ypt31/32 (Rab11) at the late Golgi/-Golgi network (TGN). This Rab conversion has been attributed to GTPase-activating protein (GAP) cascades in which Ypt31/32 recruits the Rab-GAPs Gyp1 and Gyp6 to inactivate Ypt1 and Ypt6, respectively. Here we report that Rab transition at the TGN involves additional layers of regulation. We provide new evidence confirming the TRAPPII complex as an important regulator of Ypt6 inactivation and uncover an unexpected role of the Arf1 GTPase in recruiting Gyp1 to drive Ypt1 inactivation at the TGN. Given its established role in directly recruiting TRAPPII to the TGN, Arf1 is therefore a master regulator of Rab conversion on maturing Golgi compartments.
Rab家族GTP酶是膜运输的关键组织者，并作为细胞器身份的标志物发挥作用。因此，Rab GTP酶通常占据特定的膜结构域，并且存在防止不同Rab结构域不适当混合的机制。酵母高尔基体复合物可分为两个广泛的Rab结构域：Ypt1（Rab1）和Ypt6（Rab6）存在于早期/中间高尔基体，并在晚期高尔基体/反式高尔基体网络（TGN）处急剧转变为Ypt31/32（Rab11）。这种Rab转换归因于GTP酶激活蛋白（GAP）级联反应，其中Ypt31/32招募Rab-GAPs Gyp1和Gyp6分别使Ypt1和Ypt6失活。在这里，我们报告TGN处的Rab转换涉及额外的调控层面。我们提供了新的证据，证实TRAPPII复合物是Ypt6失活的重要调节因子，并揭示了Arf1 GTP酶在招募Gyp1以驱动TGN处Ypt1失活中的意外作用。鉴于其在直接将TRAPPII招募到TGN中的既定作用，因此Arf1是成熟高尔基体区室中Rab转换的主要调节因子。
