NDR Kinase Sid2 Drives Anillin-like Mid1 from the Membrane to Promote Cytokinesis and Medial Division Site Placement.
NDR Kinase Sid2 Drives Anillin-like Mid1 from the Membrane to Promote Cytokinesis and Medial Division Site Placement.
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NDR 激酶 Sid2 从膜上驱动 Anillin 样 Mid1，以促进细胞分裂和内侧分裂位点放置。
DOI：
10.1016/j.cub.2019.01.075
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Gould,KathleenL
中科院分区：
文献类型：
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作者：
Willet,AlainaH;DeWitt,AshleyK;Beckley,JanelR;Clifford,DawnM;Gould,KathleenL
在动物和真菌中，肌动球蛋白收缩环 (CR) 的收缩促进胞质分裂 [1]。在粟酒裂殖酵母中，CR 在有丝分裂期间从称为节点的内侧细胞皮层的蛋白质簇形成中间细胞 [2]。类苯胺蛋白 Mid1 定位于节点，是中间细胞 CR 组装所必需的 [3]。当 CR 收缩开始时，Mid1 离开分裂部位。 Mid1 如何解离以及该步骤对于细胞因子进展是否重要尚不清楚。分隔启动网络 (SIN) 类似于多细胞生物的 Hippo 通路，是一个信号级联，触发节点分散、CR 组装和收缩以及隔膜形成 [4, 5]。我们报告说，末端 SIN 激酶 Sid2 [6] 会磷酸化 Mid1，以在 CR 收缩开始时驱动其从皮质中去除。不能被 Sid2 磷酸化的 Mid1 突变体在胞质分裂期间保留皮质，以依赖于 SAD 激酶 Cdr2 的方式在细胞分裂后在间期节点中过度积累，推进 G2/M 转变，提前将其他 CR 成分招募到节点，将 Cdr2 异常拉入 CR，并降低 CR 成熟和收缩的速率。当与影响节点组装或拆卸的cdr2突变体结合时，会导致分裂位点定位的严重缺陷。我们的研究结果确定 Mid1 是 SIN 介导的分裂位点重塑以实现有效胞质分裂的关键 Sid2 底物，并提供了节点用于整合协调细胞周期进程和胞质分裂的信号的证据。
In animals and fungi, cytokinesis is facilitated by the constriction of an actomyosin contractile ring (CR) [1]. InSchizosaccharomyces pombe, the CR forms mid-cell during mitosis from clusters of proteins at the medial cell cortex called nodes [2]. The anillin-like protein Mid1 localizes to nodes and is required for CR assembly at mid-cell [3]. When CR constriction begins, Mid1 leaves the division site. How Mid1 disassociates and whether this step is important for cytokinetic progression has been unknown. The septation initiation network (SIN), analogous to the Hippo pathway of multicellular organisms, is a signaling cascade that triggers node dispersal, CR assembly and constriction, and septum formation [4, 5]. We report that the terminal SIN kinase, Sid2 [6], phosphorylates Mid1 to drive its removal from the cortex at CR constriction onset. A Mid1 mutant that cannot be phosphorylated by Sid2 remains cortical during cytokinesis, over-accumulates in interphase nodes following cell division in a manner dependent on the SAD kinase Cdr2, advances the G2/M transition, precociously recruits other CR components to nodes, pulls Cdr2 aberrantly into the CR, and reduces rates of CR maturation and constriction. When combined withcdr2mutants that affect node assembly or disassembly, gross defects in division site positioning result. Our findings identify Mid1 as a key Sid2 substrate for SIN-mediated remodeling of the division site for efficient cytokinesis and provide evidence that nodes serve to integrate signals coordinating cell cycle progression and cytokinesis.