Instituto de Biología Funcional y Genómica, CSIC/Universidad de Salamanca and Departamento de Microbiología y Genética, Universidad de Salamanca, C/Zacarías González, s/n, 37007 Salamanca, Spain.
Int J Mol Sci. 2022 Nov 11;23(22):13888. doi: 10.3390/ijms232213888.
Rho1p is a membrane-associated protein that belongs to the Rho family of small GTPases. These proteins coordinate processes such as actin remodelling and polarised secretion to maintain the shape and homeostasis of yeast cells. In response to extracellular stimuli, Rho1p undergoes conformational switching between a guanosine triphosphate (GTP)-bound active state and a guanosine diphosphate (GDP)-bound inactive state. Cycling is improved with guanine nucleotide exchange factor (GEF) activity necessary to activate signalling and GTPase activating protein (GAP) activity required for subsequent signal depletion. This review focuses on fission yeast Rho1p GEFs, Rgf1p, Rgf2p, and Rgf3p that belong to the family of DH-PH domain-containing Dbl-related GEFs. They are multi-domain proteins that detect biological signals that induce or inhibit their catalytic activity over Rho1p. Each of them activates Rho1p in different places and times. Rgf1p acts preferentially during polarised growth. Rgf2p is required for sporulation, and Rgf3p plays an essential function in septum synthesis. In addition, we outline the noncanonical roles of Rho1p-GEFs in genomic instability.
Rho1p 是一种膜相关蛋白，属于 Rho 家族的小 GTP 酶。这些蛋白质协调肌动蛋白重塑和极化分泌等过程，以维持酵母细胞的形状和内稳态。在外源刺激下，Rho1p 在鸟苷三磷酸（GTP）结合的活性状态和鸟苷二磷酸（GDP）结合的非活性状态之间发生构象转换。通过鸟嘌呤核苷酸交换因子（GEF）的活性来改善循环，该活性对于激活信号转导和 GTP 酶激活蛋白（GAP）的活性是必需的，后者用于随后的信号耗竭。本篇综述专注于裂殖酵母 Rho1p GEFs，即属于 DH-PH 结构域包含的 Dbl 相关 GEFs 家族的 Rgf1p、Rgf2p 和 Rgf3p。它们是多结构域蛋白，能够检测诱导或抑制其对 Rho1p 的催化活性的生物信号。它们中的每一个都在不同的地点和时间激活 Rho1p。Rgf1p 在极化生长期间优先发挥作用。Rgf2p 是孢子形成所必需的，而 Rgf3p 在隔膜合成中发挥着重要作用。此外，我们还概述了 Rho1p-GEFs 在基因组不稳定性中的非典型作用。
