Matheos Dina, Metodiev Metodi, Muller Eric, Stone David, Rose Mark D
Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
J Cell Biol. 2004 Apr;165(1):99-109. doi: 10.1083/jcb.200309089. Epub 2004 Apr 5.
During mating, budding yeast cells reorient growth toward the highest concentration of pheromone. Bni1p, a formin homologue, is required for this polarized growth by facilitating cortical actin cable assembly. Fus3p, a pheromone-activated MAP kinase, is required for pheromone signaling and cell fusion. We show that Fus3p phosphorylates Bni1p in vitro, and phosphorylation of Bni1p in vivo during the pheromone response is dependent on Fus3p. fus3 mutants exhibited multiple phenotypes similar to bni1 mutants, including defects in actin and cell polarization, as well as Kar9p and cytoplasmic microtubule localization. Disruption of the interaction between Fus3p and the receptor-associated Galpha subunit caused similar mutant phenotypes. After pheromone treatment, Bni1p-GFP and Spa2p failed to localize to the cortex of fus3 mutants, and cell wall growth became completely unpolarized. Bni1p overexpression suppressed the actin assembly, cell polarization, and cell fusion defects. These data suggest a model wherein activated Fus3p is recruited back to the cortex, where it activates Bni1p to promote polarization and cell fusion.
在交配过程中,出芽酵母细胞会将生长方向重新定向至信息素浓度最高的地方。Bni1p是一种formin同源物,通过促进皮质肌动蛋白电缆组装来实现这种极化生长。Fus3p是一种由信息素激活的丝裂原活化蛋白激酶,参与信息素信号传导和细胞融合。我们发现,Fus3p在体外可使Bni1p磷酸化,且在信息素应答过程中,Bni1p在体内的磷酸化依赖于Fus3p。fus3突变体表现出多种与bni1突变体相似的表型,包括肌动蛋白和细胞极化缺陷,以及Kar9p和细胞质微管定位异常。Fus3p与受体相关的Gα亚基之间相互作用的破坏会导致类似的突变体表型。经信息素处理后,Bni1p-GFP和Spa2p无法定位于fus3突变体的皮质,细胞壁生长变得完全无极化。Bni1p的过表达抑制了肌动蛋白组装、细胞极化和细胞融合缺陷。这些数据提示了一种模型,即活化的Fus3p被招募回皮质,在那里它激活Bni1p以促进极化和细胞融合。