Pheromone-induced morphogenesis and gradient tracking are dependent on the MAPK Fus3 binding to Gα.

Pheromone-induced morphogenesis and gradient tracking are dependent on the MAPK Fus3 binding to Gα.
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DOI:
10.1091/mbc.e15-03-0176
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发表时间:
2015-09-15
影响因子:
3.3
通讯作者:
Elston TC
Elston TC
中科院分区:
生物学3区
文献类型:
--
作者:
Errede B;Vered L;Ford E;Pena MI;Elston TC

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发现MAPK Fus 3在酵母的交配反应中具有独特的作用。特别是,Fus 3与G蛋白α亚基的相互作用是形态发生和梯度跟踪所必需的,并且抑制了信息素响应细胞群体中交配和趋化性命运之间的细胞间变异性。丝裂原活化蛋白激酶(MAPK)途径控制许多细胞过程,包括分化和增殖。这些途径通常激活具有冗余或重叠功能的MAPK亚型。然而,最近的研究揭示了MAPK亚型在分化中具有专门的非重叠作用的情况。这种专门化的机制尚未得到很好的理解。为了解决这个问题,我们试图建立独特的MAPK Fus 3在信息素诱导的交配和趋化命运的出芽酵母酿酒酵母的转换的监管机制。我们的调查揭示了一个以前不受重视的作用,作为一个有效的负调节信息素诱导的趋化性失活Fus 3。我们表明,这种抑制作用是依赖于非活性的Fus 3结合到异源三聚体G蛋白的α亚基。进一步的分析表明,催化活性的Fus 3的G-蛋白的结合是需要梯度跟踪和服务,以抑制细胞间的变异性交配和趋化性的命运在一个群体的信息素响应细胞。
Unique roles are found for the MAPK Fus3 during the mating response of yeast. In particular, the interaction of Fus3 with the G-protein α-subunit is required for morphogenesis and gradient tracking and suppresses cell-to-cell variability between mating and chemotropic fates in a population of pheromone-responding cells. Mitogen-activated protein kinase (MAPK) pathways control many cellular processes, including differentiation and proliferation. These pathways commonly activate MAPK isoforms that have redundant or overlapping function. However, recent studies have revealed circumstances in which MAPK isoforms have specialized, nonoverlapping roles in differentiation. The mechanisms that underlie this specialization are not well understood. To address this question, we sought to establish regulatory mechanisms that are unique to the MAPK Fus3 in pheromone-induced mating and chemotropic fate transitions of the budding yeast Saccharomyces cerevisiae. Our investigations reveal a previously unappreciated role for inactive Fus3 as a potent negative regulator of pheromone-induced chemotropism. We show that this inhibitory role is dependent on inactive Fus3 binding to the α-subunit of the heterotrimeric G-protein. Further analysis revealed that the binding of catalytically active Fus3 to the G-protein is required for gradient tracking and serves to suppress cell-to-cell variability between mating and chemotropic fates in a population of pheromone-responding cells.