Yeast RSC function is required for organization of the cellular cytoskeleton via an alternative PKC1 pathway.
Yeast RSC function is required for organization of the cellular cytoskeleton via an alternative PKC1 pathway.
复制标题
酵母 RSC 功能是通过替代 PKC1 途径组织细胞骨架所必需的。
DOI：
10.1093/genetics/161.2.575
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发表时间：
2002
期刊：
影响因子：
3.3
通讯作者：
Laurent,BrehonC
中科院分区：
文献类型：
--
作者：
Chai,Bob;Hsu,Jing-mei;Du,Jian;Laurent,BrehonC
RSC是一种由15种蛋白质组成的依赖于ATP的染色质重塑复合体，与SNF-Swi相关，SNF-Swi是萌芽酵母中典型的依赖于ATP的核小体重塑因子。尽管对纯化的RSC重塑核小体的机制有了深入的了解，但对RSC作用的染色体靶点或细胞途径知之甚少。为了更好地了解RSC的细胞功能，我们对编码必需的ATPase亚单位的STH1的温度敏感突变sth1-3ts的基因剂量抑制因子进行了筛选。SLg1p和Mid2p是两种I型跨膜应力传感器，它们位于蛋白激酶C(Pkc1p)的上游，是sth1-3tscells的多拷贝抑制因子。尽管th1-3ts突变体表现出pkc1途径突变体特有的缺陷(咖啡因和星形孢子素敏感性，以及一种渗透中层表型)，但只有pkc1-map激酶途径的上游成分而不是下游效应物才能抑制由th1-3ts引起的缺陷，这表明RSC在另一条依赖pkc1的途径中发挥作用。此外，sth1-3tscells在肌动蛋白细胞骨架重排中显示缺陷，并且对微管解聚药物tbz高度敏感；这些缺陷都可以被高拷贝抑制物纠正。综上所述，这些数据揭示了RSC重建器和PKC1依赖的信号之间在调节细胞结构方面的重要功能联系。
RSC is a 15-protein ATP-dependent chromatin-remodeling complex related to Snf-Swi, the prototypical ATP-dependent nucleosome remodeler in budding yeast. Despite insight into the mechanism by which purified RSC remodels nucleosomes, little is known about the chromosomal targets or cellular pathways in which RSC acts. To better understand the cellular function of RSC, a screen was undertaken for gene dosage suppressors ofsth1-3ts, a temperature-sensitive mutation inSTH1, which encodes the essential ATPase subunit. Slg1p and Mid2p, two type I transmembrane stress sensors of cell wall integrity that function upstream of protein kinase C (Pkc1p), were identified as multicopy suppressors ofsth1-3tscells. Although thesth1-3tsmutant exhibits defects characteristic ofPKC1pathway mutants (caffeine and staurosporine sensitivities and an osmoremedial phenotype), only upstream components and not downstream effectors of thePKC1-MAP kinase pathway can suppress defects conferred bysth1-3ts, suggesting that RSC functions in an alternativePKC1-dependent pathway. Moreover,sth1-3tscells display defects in actin cytoskeletal rearrangements and are hypersensitive to the microtubule depolymerizing drug, TBZ; both of these defects can be corrected by the high-copy suppressors. Together, these data reveal an important functional connection between the RSC remodeler andPKC1-dependent signaling in regulating the cellular architecture.