Transient PP2A SIP complex localization to mitotic SPBs for SIN inhibition is mediated solely by the Csc1 FHA domain.

IF 3.1 3区 生物学 Q3 CELL BIOLOGY
Molecular Biology of the Cell Pub Date : 2024-08-01 Epub Date: 2024-06-12 DOI:10.1091/mbc.E24-04-0196
Alaina H Willet, Liping Ren, Lesley A Turner, Kathleen L Gould
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引用次数: 0

Abstract

Many organisms utilize an actin- and myosin-based cytokinetic ring (CR) to help complete cytokinesis. In Schizosaccharomyces pombe, the Septation Initiation Network (SIN) promotes proper CR function and stability. The SIN is a conserved and essential signaling network consisting of a GTPase and a cascade of kinases assembled at the spindle pole body (SPB). The PP2A SIN inhibitory phosphatase (SIP) complex related to the STRIPAK phosphatase complex is one inhibitor of SIN signaling. The SIP consists of Csc1, Csc2, Csc3, Csc4, Paa1, and the phosphatase subunit Ppa3. Here, we determine that the SIP is anchored at the SPB via the Csc1 FHA domain and that constitutive SPB localization of the SIP is lethal due to persistent SIN inhibition. Disrupting SIP docking at the SPB with a point mutation within the FHA domain or eliminating phosphatase activity by introducing a point mutation within Ppa3 resulted in intact SIP complexes without SIN inhibitory function. Lastly, we defined the unique features of Ppa3 that allow it, but not two other PP2A catalytic subunits, to incorporate into the SIP. Overall, we provide insight into how the SIP complex assembles, localizes, and functions to counteract the SIN with spatiotemporal precision during cytokinesis.

瞬时 PP2A SIP 复合物定位到有丝分裂 SPB 以抑制 SIN 的过程完全由 Csc1 FHA 结构域介导。
许多生物利用基于肌动蛋白和肌球蛋白的细胞动环来帮助完成细胞分裂。在奇异酵母菌(Schizosaccharomyces pombe)中,细胞分裂起始网络(Septation Initiation Network,SIN)可促进 CR 的正常功能和稳定性。SIN 是一个保守而重要的信号网络,由聚集在纺锤极体(SPB)上的 GTPase 和激酶级联组成。与 STRIPAK 磷酸酶复合物相关的 PP2A SIN 抑制性磷酸酶(SIP)复合物是 SIN 信号传导的一个抑制因子。SIP 由 Csc1、Csc2、Csc3、Csc4、Paa1 和磷酸酶亚基 Ppa3 组成。在这里,我们确定 SIP 是通过 Csc1 FHA 结构域锚定在 SPB 上的,并且由于 SIN 的持续抑制,SIP 的组成性 SPB 定位是致命的。通过FHA结构域的点突变破坏SIP在SPB上的对接,或通过引入Ppa3的点突变消除磷酸酶活性,都会导致完整的SIP复合物没有SIN抑制功能。最后,我们确定了 Ppa3 的独特特征,即允许它(而不是其他两个 PP2A 催化亚基)结合到 SIP 中。总之,我们对 SIP 复合物如何组装、定位以及在细胞运动过程中如何在时空上精确地抵消 SIN 的功能有了深入的了解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Biology of the Cell
Molecular Biology of the Cell 生物-细胞生物学
CiteScore
6.00
自引率
6.10%
发文量
402
审稿时长
2 months
期刊介绍: MBoC publishes research articles that present conceptual advances of broad interest and significance within all areas of cell, molecular, and developmental biology. We welcome manuscripts that describe advances with applications across topics including but not limited to: cell growth and division; nuclear and cytoskeletal processes; membrane trafficking and autophagy; organelle biology; quantitative cell biology; physical cell biology and mechanobiology; cell signaling; stem cell biology and development; cancer biology; cellular immunology and microbial pathogenesis; cellular neurobiology; prokaryotic cell biology; and cell biology of disease.
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