Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
Curr Genet. 2019 Feb;65(1):119-125. doi: 10.1007/s00294-018-0874-0. Epub 2018 Aug 12.
In response to various environmental stimuli and stressors, the budding yeast Saccharomyces cerevisiae can initiate a striking morphological transition from its classic growth mode as isolated single cells to a filamentous form in which elongated cells remain connected post-cytokinesis in multi-cellular pseudohyphae. The formation of pseudohyphal filaments is regulated through an expansive signaling network, encompassing well studied and highly conserved pathways enabling changes in cell polarity, budding, cytoskeletal organization, and cell adhesion; however, changes in metabolite levels underlying the pseudohyphal growth transition are less well understood. We have recently identified a function for second messenger inositol polyphosphates (InsPs) in regulating pseudohyphal growth. InsPs are formed through the cleavage of membrane-bound phosphatidylinositol 4,5-bisphosphate (PIP), and these soluble compounds are now being appreciated as important regulators of diverse processes, from phosphate homeostasis to cell migration. We find that kinases in the InsP pathway are required for wild-type pseudohyphal growth, and that InsP species exhibit characteristic profiles under conditions promoting filamentation. Ratios of the doubly phosphorylated InsP isoforms 5PP-InsP to 1PP-InsP are elevated in mutants exhibiting exaggerated pseudohyphal growth. Interestingly, S. cerevisiae mutants deleted of the mitogen-activated protein kinases (MAPKs) Kss1p or Fus3p or the AMP-activated kinase (AMPK) family member Snf1p display mutant InsP profiles, suggesting that these signaling pathways may contribute to the regulatory mechanism controlling InsP levels. Consequently, analyses of yeast pseudohyphal growth may be informative in identifying mechanisms regulating InsPs, while indicating a new function for these conserved second messengers in modulating cell stress responses and morphogenesis.
在应对各种环境刺激和应激源时， budding yeast Saccharomyces cerevisiae 可以从其经典的单细胞生长模式惊人地转变为丝状形态，在这种形态中，细胞在细胞分裂后仍然以多细胞假菌丝的形式连接。假菌丝的形成受到广泛的信号网络的调节，包括研究充分且高度保守的途径，这些途径可改变细胞极性、出芽、细胞骨架组织和细胞黏附；然而，假菌丝生长转变所涉及的代谢物水平的变化则知之甚少。我们最近发现，第二信使肌醇多磷酸盐（InsPs）在调节假菌丝生长中具有功能。InsPs 通过膜结合的磷脂酰肌醇 4,5-二磷酸（PIP）的裂解形成，这些可溶性化合物现在被认为是调节从磷酸盐稳态到细胞迁移等多种过程的重要调节剂。我们发现，InsP 途径中的激酶对于野生型假菌丝生长是必需的，并且在促进丝状生长的条件下，InsP 种类表现出特征性的谱。在表现出过度假菌丝生长的突变体中，双磷酸化 InsP 同型物 5PP-InsP 与 1PP-InsP 的比值升高。有趣的是，缺失丝裂原活化蛋白激酶（MAPKs）Kss1p 或 Fus3p 或 AMP 激活蛋白激酶（AMPK）家族成员 Snf1p 的 S. cerevisiae 突变体显示出突变的 InsP 谱，表明这些信号通路可能有助于控制 InsP 水平的调节机制。因此，对酵母假菌丝生长的分析可能有助于识别调节 InsPs 的机制，同时表明这些保守的第二信使在调节细胞应激反应和形态发生方面具有新的功能。
