A homologue of the human STRIPAK complex controls sexual development in fungi

A homologue of the human STRIPAK complex controls sexual development in fungi
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DOI:
10.1111/j.1365-2958.2012.08024.x
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发表时间:
2012-04-01
影响因子:
3.6
通讯作者:
Kueck, Ulrich
Kueck, Ulrich
中科院分区:
生物学2区
文献类型:
--
作者:
Bloemendal, Sandra;Bernhards, Yasmine;Kueck, Ulrich

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真菌的性发育是一个复杂的过程,涉及新细胞类型和组织的产生,这是所有真核生物的重要步骤。在子囊菌大孢囊霉不育突变体的表征导致了一些蛋白质参与性发育,但这些蛋白质之间的联系仍然缺失。使用串联亲和纯化/质谱法相结合的方法,我们表明在体内协会的发展蛋白PRO22与PRO 11,同源的哺乳动物纹状体,SmPP 2AA,支架蛋白磷酸酶2A亚基。进一步的实验将蛋白质网络扩展到已知参与性发育的假定激酶激活剂SmMOB 3。广泛的酵母双杂交研究使我们能够查明参与蛋白质相互作用的功能域。我们第一次表明,一些已知的因素与新的组件相关联,在体内形成一个高度保守的多亚基复合物。引人注目的是,在人类中已经描述了类似的复合物,但是这种所谓的纹状体相互作用磷酸酶和激酶(STRIPAK)复合物的功能在很大程度上是未知的。In S.大孢霉中,PRO 11和PRO22的截短导致性发育和细胞融合的明显缺陷,表明真菌STRIPAK复合体在这两个过程中的作用。
Sexual development in fungi is a complex process involving the generation of new cell types and tissues an essential step for all eukaryotic life. The characterization of sterile mutants in the ascomycete Sordaria macrospora has led to a number of proteins involved in sexual development, but a link between these proteins is still missing. Using a combined tandem-affinity purification/mass spectrometry approach, we showed in vivo association of developmental protein PRO22 with PRO11, homologue of mammalian striatin, and SmPP2AA, scaffolding subunit of protein phosphatase 2A. Further experiments extended the protein network to the putative kinase activator SmMOB3, known to be involved in sexual development. Extensive yeast two-hybrid studies allowed us to pinpoint functional domains involved in proteinprotein interaction. We show for the first time that a number of already known factors together with new components associate in vivo to form a highly conserved multi-subunit complex. Strikingly, a similar complex has been described in humans, but the function of this so-called striatin interacting phosphatase and kinase (STRIPAK) complex is largely unknown. In S. macrospora, truncation of PRO11 and PRO22 leads to distinct defects in sexual development and cell fusion, indicating a role for the fungal STRIPAK complex in both processes.