Department Biology II, Ludwig-Maximilians University, Planegg-Martinsried, Munich 82152, Germany.
Department Biology II, Ludwig-Maximilians University, Planegg-Martinsried, Munich 82152, Germany.
Cell Rep. 2021 Mar 2;34(9):108805. doi: 10.1016/j.celrep.2021.108805.
During cell division, the guanine nucleotide exchange factor (GEF) ECT2 activates RhoA in a narrow zone at the cell equator in anaphase. ECT2 consists of three BRCT domains (BRCT0, 1, and 2), a catalytic GEF, and a pleckstrin homology (PH) domain. How the conserved BRCT domains spatially and temporally control ECT2 activity remains unclear. We reveal that each BRCT domain makes distinct contributions to the ECT2 function. We find that BRCT0 contributes to, and BRCT1 is essential for, ECT2 activation in anaphase. BRCT2 integrates two functions: GEF inhibition and RACGAP1 binding, which together limit ECT2 activity to a narrow zone at the cell equator. BRCT2-dependent control of active RhoA zone dimension functions in addition to the inhibitory signal of the astral microtubules. Our analysis provides detailed mechanistic insights into how ECT2 activity is regulated and how that regulation ensures, together with other signaling pathways, successful cell division.
在细胞分裂过程中，鸟嘌呤核苷酸交换因子（GEF）ECT2 在后期赤道处的狭窄区域激活 RhoA。ECT2 由三个 BRCT 结构域（BRCT0、1 和 2）、一个催化 GEF 和一个pleckstrin 同源（PH）结构域组成。然而，BRCT 结构域如何在空间和时间上控制 ECT2 活性仍不清楚。我们揭示了每个 BRCT 结构域对 ECT2 功能的独特贡献。我们发现 BRCT0 有助于 ECT2 在后期的激活，BRCT1 对于 ECT2 的激活是必不可少的。BRCT2 整合了两种功能：GEF 抑制和 RACGAP1 结合，这两种功能共同将 ECT2 的活性限制在赤道处的狭窄区域。BRCT2 依赖性的控制活性 RhoA 区的维度功能除了星体微管的抑制信号外还有作用。我们的分析提供了关于 ECT2 活性如何被调节的详细机制见解，以及这种调节如何与其他信号通路一起确保细胞分裂的成功。
