Profilin-mediated competition between capping protein and formin Cdc12p during cytokinesis in fission yeast

Profilin-mediated competition between capping protein and formin Cdc12p during cytokinesis in fission yeast
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DOI:
10.1091/mbc.e04-09-0781
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发表时间:
2005-05-01
影响因子:
3.3
通讯作者:
Pollard, TD
Pollard, TD
中科院分区:
生物学3区
文献类型:
--
作者:
Kovar, DR;Wu, JQ;Pollard, TD

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裂殖酵母加帽蛋白SpCP是两个亚基(Acp1p和Acp2p)组成的异二聚体,它结合肌动蛋白丝的正端。acp1和acp2对于细胞活力都不是必需的,但缺乏其中一个或两个亚基的细胞在应激条件下会有胞质分裂缺陷,这些应激条件包括高温、渗透胁迫,或者与众多对胞质分裂重要的基因的轻微突变共同作用。当收缩环收缩和解体时会出现缺陷,导致细胞分离延迟。遗传和生化相互作用表明,胞质分裂成蛋白Cdc12p在细胞中与加帽蛋白竞争肌动蛋白丝的正端。acp2的缺失部分抑制了温度敏感型cdc12 - 112细胞的胞质分裂缺陷,并且加帽蛋白的适度过表达会杀死cdc12 - 112细胞。在生化方面,前纤维蛋白对由Cdc12p和加帽蛋白加帽的丝有相反的作用。前纤维蛋白使由加帽蛋白加帽的肌动蛋白丝解聚,但允许由Cdc12p加帽的丝在其正端生长。一旦与正端结合,Cdc12p或加帽蛋白都会阻止对方影响该端的聚合。鉴于加帽蛋白比Cdc12p晚20分钟到达分裂位点,加帽蛋白可能会缓慢取代肌动蛋白丝正端上的Cdc12p,为收缩环收缩过程中的丝解体做准备。
Fission yeast capping protein SpCP is a heterodimer of two subunits (Acp1p and Acp2p) that binds actin filament barbed ends. Neither acp1 nor acp2 is required for viability, but cells lacking either or both subunits have cytokinesis defects under stressful conditions, including elevated temperature, osmotic stress, or in combination with numerous mild mutations in genes important for cytokinesis. Defects arise as the contractile ring constricts and disassembles, resulting in delays in cell separation. Genetic and biochemical interactions show that the cytokinesis formin Cdc12p competes with capping protein for actin filament barbed ends in cells. Deletion of acp2 partly suppresses cytokinesis defects in temperature-sensitive cdc12-112 cells and mild overexpression of capping protein kills cdc12-112 cells. Biochemically, profilin has opposite effects on filaments capped with Cdc12p and capping protein. Profilin depolymerizes actin filaments capped by capping protein but allows filaments capped by Cdc12p to grow at their barbed ends. Once associated with a barbed end, either Cdc12p or capping protein prevents the other from influencing polymerization at that end. Given that capping protein arrives at the division site 20 min later than Cdc12p, capping protein may slowly replace Cdcl2p on filament barbed ends in preparation for filament disassembly during ring constriction.