Septin-dependent assembly of a cell cycle-regulatory module in Sacharomyces cerevisiae
Septin-dependent assembly of a cell cycle-regulatory module in Sacharomyces cerevisiae
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DOI：
10.1128/mcb.20.11.4049-4061.2000
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发表时间：
2000-06-01
影响因子：
5.3
通讯作者：
Lew, DJ
中科院分区：
文献类型：
--
作者：
Longtine, MS;Theesfeld, CL;Lew, DJ
酿酒酵母septin突变体具有多效性缺陷，其包括异常伸长芽的形成。这种芽形态至少部分地由Cdc 28 p抑制性激酶Swe 1 p施加的细胞周期延迟引起。其他三个基因（GIN 4，编码与粟酒裂殖酵母有丝分裂诱导剂Nim 1 p相关的激酶; CLA 4，编码p21激活的激酶;和NAP 1，编码Clb 2 p相互作用蛋白）的突变也会产生与Sw 1 p相关的septin组织的扰动依赖性细胞周期延迟。gin 4，cla 4和nap 1突变的影响是累加的，表明这些蛋白质通过至少部分独立的途径促进正常的隔蛋白组织。与此相反，在S. cerevisiae、Hsl 1 p和Kcc 4p对septin组织没有可检测的影响。然而，HSL 1的缺失，但不是KCC 4，在某些条件下产生细胞周期延迟，这种延迟似乎反映了Hsl 1 p在调节Swe 1 p的直接作用。如前所述，Swe 1 p在形态发生检查点中起核心作用，该检查点延迟细胞周期以响应芽形成中的缺陷。Swe 1 p在G（2）/M期降解之前定位于母芽颈的细胞核和子体侧。Swe 1 p的颈部定位及其降解都需要Hsl 1 p及其结合伴侣Hsl 7 p，这两者都与Swe 1 p在颈部的子体侧共定位。这种定位在Septin结构紊乱的突变体中丢失，表明Hsl 1 p和Hsl 7 p从颈部的释放可能降低了它们抑制Swe 1 p的能力，从而导致在此类突变体中观察到的G（2）延迟。与此相反，治疗扰乱肌动蛋白组织Hsl 1 p和Hsl 7 p本地化的影响不大，这表明，这种治疗必须稳定Swe 1 p的另一种机制。Swe 1 p降解对Hsl 1 p-Hsl 7 p-Swe 1 p模块定位于仅存在于出芽细胞中的位点的明显依赖性可能构成了当不再需要形态发生检查点时使其失活的机制（即，在芽形成之后）。
Saccharomyces cerevisiae septin mutants have pleiotropic defects, which include the formation of abnormally elongated buds. This bud morphology results at least in part from a cell cycle delay imposed by the Cdc28p-inhibitory kinase Swe1p. Mutations in three other genes (GIN4, encoding a kinase related to the Schizosaccharomyces pombe mitotic inducer Nim1p; CLA4, encoding a p21-activated kinase; and NAP1, encoding a Clb2p-interacting protein) also produce perturbations of septin organization associated with an Swe1p-dependent cell cycle delay. The effects of gin4, cla4, and nap1 mutations are additive, indicating that these proteins promote normal septin organization through pathways that are at least partially independent. In contrast, mutations affecting the other two Nim1p-related kinases in S. cerevisiae, Hsl1p and Kcc4p, produce no detectable effect on septin organization. However, deletion of HSL1, but not of KCC4, did produce a cell cycle delay under some conditions; this delay appears to reflect a direct role of Hsl1p in the regulation of Swe1p. As shown previously, Swe1p plays a central role in the morphogenesis checkpoint that delays the cell cycle in response to defects in bud formation. Swe1p is localized to the nucleus and to the daughter side of the mother bud neck prior to its degradation in G(2)/M phase. Both the neck localization of Swe1p and its degradation require Hsl1p and its binding partner Hsl7p, both of which colocalize with Swe1p at the daughter side of the neck. This localization is lost in mutants with perturbed septin organization, suggesting that the release of Hsl1p and Hsl7p from the neck may reduce their ability to inactivate Swe1p and thus contribute to the G(2) delay observed in such mutants. In contrast, treatments that perturb actin organization have little effect on Hsl1p and Hsl7p localization, suggesting that such treatments must stabilize Swe1p by another mechanism. The apparent dependence of Swe1p degradation on localization of the Hsl1p-Hsl7p-Swe1p module to a site that exists only in budded cells may constitute a mechanism for deactivating the morphogenesis checkpoint when it is no longer needed (i.e., after a bud has formed).