Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p.

Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p.
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DOI:
10.1083/jcb.200109062
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发表时间:
2002-01-21
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Lew DJ
Lew DJ
中科院分区:
其他
文献类型:
--
作者:
Gladfelter AS;Bose I;Zyla TR;Bardes ES;Lew DJ

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在芽殖酵母细胞周期开始时,GTdR Cdc 42 p促进在未来芽出现的位点组装一个septins环。在这里,我们对在septin组织中表现出特定缺陷的cdc 42突变体进行了分析,这确定了Cdc 42 p在septin环组装中对GTP水解的重要作用。突变体表现出缺陷的基础或刺激GTP水解,和隔蛋白的错误组织被抑制过表达的Cdc 42 p GTP酶激活蛋白(GAP)。其他已知影响GTP水解Cdc 42 p的突变体也会导致septin的错误组织,如Cdc 42 p GAP的缺失。在执行其在肌动蛋白极化和转录激活中的作用时,GTP-Cdc 42 p被认为通过激活和/或招募效应子到极化位点来发挥作用。由于septin特异性等位基因在GTP水解中的缺陷,GTP-Cdc 42 p的过量积累可能导致效应子的非生理性激活,干扰septin组装。然而,隔蛋白特异性cdc 42突变体的隐性和剂量敏感性遗传行为与这种类型的显性干扰引起的隔蛋白缺陷不一致。相反,我们建议,塞普丁环的组装涉及重复循环的GTP加载和GTP水解Cdc 42 p。这些结果表明,一个单一的GTP酶,Cdc 42 p,可以作为一个ras样GTP依赖性的“开关”打开效应器或作为EF-Tu样的“组装因子”使用GTP酶循环组装一个大分子结构。
At the beginning of the budding yeast cell cycle, the GTPase Cdc42p promotes the assembly of a ring of septins at the site of future bud emergence. Here, we present an analysis of cdc42 mutants that display specific defects in septin organization, which identifies an important role for GTP hydrolysis by Cdc42p in the assembly of the septin ring. The mutants show defects in basal or stimulated GTP hydrolysis, and the septin misorganization is suppressed by overexpression of a Cdc42p GTPase-activating protein (GAP). Other mutants known to affect GTP hydrolysis by Cdc42p also caused septin misorganization, as did deletion of Cdc42p GAPs. In performing its roles in actin polarization and transcriptional activation, GTP-Cdc42p is thought to function by activating and/or recruiting effectors to the site of polarization. Excess accumulation of GTP-Cdc42p due to a defect in GTP hydrolysis by the septin-specific alleles might cause unphysiological activation of effectors, interfering with septin assembly. However, the recessive and dose-sensitive genetic behavior of the septin-specific cdc42 mutants is inconsistent with the septin defect stemming from a dominant interference of this type. Instead, we suggest that assembly of the septin ring involves repeated cycles of GTP loading and GTP hydrolysis by Cdc42p. These results suggest that a single GTPase, Cdc42p, can act either as a ras-like GTP-dependent “switch” to turn on effectors or as an EF-Tu–like “assembly factor” using the GTPase cycle to assemble a macromolecular structure.
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影响因子: 7.8
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