Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, China.
PLoS Genet. 2019 Jun 13;15(6):e1008206. doi: 10.1371/journal.pgen.1008206. eCollection 2019 Jun.
The septation initiation network (SIN), composed of a conserved SepH (Cdc7p) kinase cascade, plays an essential role in fungal cytokinesis/septation and conidiation for asexual reproduction, while the mitogen-activated protein kinase (MAPK) pathway depends on successive signaling cascade phosphorylation to sense and respond to stress and environmental factors. In this study, a SepH suppressor-PomA in the filamentous fungus A. nidulans is identified as a negative regulator of septation and conidiation such that the pomA mutant is able to cure defects of sepH1 in septation and conidiation and overexpression of pomA remarkably suppresses septation. Under the normal cultural condition, SepH positively regulates the phosphorylation of MAPK-HogA, while PomA reversely affects this process. In the absence of PbsB (MAPKK, a putative upstream member of HogA), PomA and SepH are unable to affect the phosphorylation level of HogA. Under the osmostress condition, the induced phosphorylated HogA is capable of bypassing the requirement of SepH, a key player for early events during cytokinesis but not for MobA/SidB, the last one in the core SIN protein kinase cascade, indicating the osmotic stimuli-induced septation is capable of bypassing requirement of SepH but unable to bypass the whole SIN requirement. Findings demonstrate that crosstalk exists between the SIN and MAPK pathways. PomA and SepH indirectly regulate HogA phosphorylation through affecting HogA-P upstream kinases.
隔膜起始网络(SIN)由保守的 SepH(Cdc7p)激酶级联组成,在真菌胞质分裂/隔膜形成和无性繁殖的分生孢子形成中起着至关重要的作用,而丝裂原激活的蛋白激酶(MAPK)途径依赖于连续的信号级联磷酸化来感知和响应应激和环境因素。在这项研究中,丝状真菌 A. nidulans 中的 SepH 抑制因子-PomA 被鉴定为隔膜形成和分生孢子形成的负调节剂,使得 pomA 突变体能修复 sepH1 在隔膜形成和分生孢子形成中的缺陷,而过表达 pomA 则显著抑制隔膜形成。在正常培养条件下,SepH 正向调节 MAPK-HogA 的磷酸化,而 PomA 则反向影响这一过程。在缺乏 PbsB(MAPKK,HogA 的一个假定上游成员)的情况下,PomA 和 SepH 都无法影响 HogA 的磷酸化水平。在渗透压应激条件下,诱导的磷酸化 HogA 能够绕过隔膜形成的 SepH 的要求,SepH 是胞质分裂早期事件的关键参与者,但不是 MobA/SidB 的要求,后者是核心 SIN 蛋白激酶级联中的最后一个,这表明渗透压刺激诱导的隔膜形成能够绕过 SepH 的要求,但不能绕过整个 SIN 的要求。研究结果表明,SIN 和 MAPK 途径之间存在串扰。PomA 和 SepH 通过影响 HogA-P 上游激酶间接调节 HogA 磷酸化。