You will be presented with the abstract, introduction, and discussion section from a biomedical research article. Your task is to create a summary that a layperson can understand, capturing the essence of the research article. Keep essential scientific terms, but ensure that the language remains clear and the concepts are explained in an uncomplicated manner.

Title: A new identified suppressor of Cdc7p/SepH kinase, PomA, regulates fungal asexual reproduction via affecting phosphorylation of MAPK-HogA}
Article:
Abstract:
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.
Introduction:
The filamentous fungus contains a mycelium of multinucleated cells that are partitioned by septa, and timely cytokinesis and septation is essential for hyphal growth and conidiation[1, 2]. Conidia are the primary means of asexual reproduction and dispersal in the environment for a variety of fungi[3–5]. Generally, fungal cells respond to environmental stimuli through signaling pathways often involving kinase cascades that transmit external cellular signals to the nucleus[6–8]. Genetic analyses have reported that the model filamentous fungus Aspergillus nidulans and Schizosaccharomyces pombe have components of the septum initiation network( SIN), and septum formation requires the assembly of a septal band composed of a dynamic protein complex that is dependent upon conserved core SIN components including three protein kinases( SepH/Cdc7p, SidA/Sid1p and SidB/Sid2p), and their regulatory partners( SpgA/Spg1p, Cdc14p and MobA/Mob1p), respectively[2, 9, 10]. Notably, downregulation of the serine/threonine protein kinase SepH cascade in A. nidulans would abolish septation and conidiation, its hyperactivation of it would induce the formation of multiple septa. Thus, SepH is a positive regulator of the SIN that triggers septation/conidiation in A. nidulans[9]. However, whether negative regulators exist for conidiation is elusive. In addition, individual cell signaling pathways can communicate with each other, thereby building a complex network to ultimately control gene expression and other cellular functions[11]. In all eukaryotic kingdoms, mitogen-activated protein kinases( MAPKs) play critical roles in cellular responses to environmental cues[12]. These MAPKs are activated by phosphorylation at highly conserved threonine and tyrosine residues[13] in response to specific inputs, leading to their accumulation in the nucleus and the activation of their downstream targets[14]. Three-tiered core signaling modules, including MAPK kinase kinases( MAPKKK), MAPK kinases( MAPKK) and MAPK, are included in the MAPK signaling pathway[12, 15]. Cells respond to different external environment stresses, including pH, light signaling, and osmotic or oxidative stress, by phosphorylating the kinase cascade to activate the MAPK signaling pathway[11, 14, 16, 17]. Thereafter, MAPK is phosphorylated and shuttles into nuclei upon stimuli to trigger gene expression. Thus, reversible protein phosphorylation plays a critical role in the regulation of virtually all eukaryotic biological processes, and the MAPK signaling pathway plays a crucial role in different organisms from mammals to fungi. In mammalian cells, the MAPK signaling pathway is critical for normal immune and inflammatory responses and contributes to cell cycle or cytoskeleton remodeling[18]. In model yeasts, the MAPK signaling pathway involves many biological processes, including cell wall integrity, cell separation and the regulation of mitotic spindle disassembly[15, 19]. In most filamentous fungi, the high-osmolarity glycerol( HOG) gene hogA, which encodes a MAPK that sense osmotic and oxidative stress, is required for hyphal growth and conidiation under osmotic stress culture conditions[14, 20]. Moreover, in the opportunistic fungal pathogen A. fumigatus, the high-osmolarity glycerol( HOG) MAPK signaling pathway is crucial for virulence and conidiation under stress conditions[12, 21]. Therefore, both the SepH-SIN kinase cascade and the HOG-MAPK pathway are involved in cell growth and reproduction by regulating reversible protein phosphorylation. However, whether crosstalk between the SIN cascade and the HOG-MAPK pathway exists remains unknown. Through UV mutagenesis, our previous studies identified antagonizing components of the SepH kinase cascade[22]. However, this complex protein cascade has not yet been dissected since the majority of mutants isolated by UV mutagenesis have no clear phenotype. Therefore, it is difficult to confirm these related mutations in the complementation assay by transforming a whole-genome library since a critical barrier in forward genetics is to verify gene functions with no detectable phenotypes. With the development of next-generation sequencing( NGS), it is possible to identify these mutations by comparing single nucleotide polymorphisms( SNPs) between mutants and wild type which all have the same parental genetic background. Based on these approaches, in this study, through backcross techniques combined with a new mutation comparison analysis of NGS, a putative protein kinase, PomA, a suppressor of SepH, was identified to be involved in septation and conidiation. Moreover, quantitative phosphoproteomics revealed that deletion of pomA causes activation of the HOG MAPK signaling pathway.
Discussion:
In this study, by SNPs comparison and the backcross techniques between the mutant and the same parental background wild-type strain, we isolated a new suppressor of SepH( an SIN cascade component), PomA. Our principal conclusions are as follows. First, a putative protein kinase, PomA, in A. nidulans localized with a spindle pole body-like pattern and the tips of hyphal cells, as a suppressor of SepH, is involved in septation and conidiation such that lack of PomA cures defects of septation and conidiation in sepH1 while overexpression of PomA remarkably abolishes septation and condiation. Second, SepH positively regulates the phosphorylation of HogA, while PomA reversely affects this process. Third, the phosphorylation of HogA induced by osmotic stress bypasses the requirement of SepH to fulfill septation and conidiation. We demonstrated that crosstalk exists between the SIN and MAPK pathways such that PomA and SepH indirectly regulate HogA phosphorylation through affecting HogA-P upstream kinases. Several lines of evidence indicate that SepH, a homolog of serine-threonine kinase Cdc7p in fission yeast, is a main positive regulator in the SIN in A. nidulans[9, 30, 31]. The sepH1 mutant with completely abolished septation and fluffy colony phenotypes was previously isolated by screening in temperature-sensitive cytokinesis mutants[9, 22, 31]. Pom1, a dual-specificity tyrosine phosphorylation-regulated kinase in S. pombe[32], inhibits the SAD-like kinase Cdr2 and Mid1/anillin to negatively control cell division plane positioning and restricts the cell middle cortical cytokinetic ring precursor nodes through an unknown mechanism[32–35]. The Pom1 mutants divide at a significantly shorter size[32] than wild type cells and some mutants display an abnormal growth axis, resulting in angled and branched cells[36]. These findings suggest that Pom1 in S. pombe is required for the timing of cytokinesis and for normal polarized cell growth[32, 34, 36–39]. However, the functions of the Pom1 homolog PomA in A. nidulans have not yet been reported. Our findings suggest that the loss of pomA causes no detectable difference in hyphal cell polarized growth or in septation compared with the wild type strain, even though PomA contains the SPB and exhibits cell tip localization patterns that are similar to those of Pom1( Fig 3C–3F). This phenomenon may also suggest other alternative candidates to bypass the requirement for polarity growth and for septation in the absence of PomA. In contrast, the overexpression of pomA caused significantly reduced colony growth accompanied with abolished septation/conidiation( Fig 3D and 3G), suggesting that PomA is a negative regulator of this process and also implying PomA is a potential efficient inhibitor for conidiation. Our findings demonstrated that osmotic stressors NaCl or KCl were able to induce septation and conidiation regardless of the absence or presence of the SIN component SepH( Fig 5C). These data indicate that when fungi sense environmental stresses, they bypass the originally required SIN protein cascade-SepH to fit the environmental niches by highly expressing phosphorylated HogA. These findings also suggest that phosphorylated HogA plays important roles in septation and conidiation. Accordingly, loss of the SIN component SepH caused reduced expression of HogA-P( Fig 5A and 5F) with completely abolished septation/conidiation, while the deletion of PomA rescued these defects induced by defects of sepH as well as suppressing decreased HogA-P expression in the sepH1 pomA double mutant( Fig 5F). However, we still could not exclude another possibility for a full-length SepH protein may be also required for the osmotic stimuli-induced septation since sepH1 is a temperature-sensitive cytokinesis mutant not a null mutant. Our new findings also suggest that the HogA phosphorylation was able to bypass requirement of SepH but not for MobA/SidB since deletion of pomA was unable to rescue septation when expression of MobA was turn-off even under the osmotic stress cultural condition. SepH, a key player for early events during cytokinesis while SidB is the last kinase in the core SIN protein kinase cascade. These findings demonstrate that MobA and SidB are required for septation and may also imply HogA-P might be an upstream member of MobA/SidB for septation as shown in the working model of Fig 6. Taken together, SepH and PomA were able to retroregulate the phosphorylation of HogA for septation and conidiation under non-osmotic stress stimulus conditions. PomA and SepH indirectly affect the expression of HogA. SepH, a main kinase of the SIN, regulates septation/cytokinesis by phosphorylating downstream targets[2]. However, PomA is also a putative kinase and, similar to other serine/threonine protein kinases, the catalytic domain( S-TKc) is included. Thus, we hypothesize that PomA suppresses the defects of SepH indirectly by phosphorylating other proteins. In the absence of PbsB( MAPKK, a putative upstream member of HogA), HogA phosphorylation is completely abolished such that deletion of PomA or SepH is unable to rescue or change the phosphorylation level of HogA. Thus, we conclude that PomA and SepH indirectly regulate HogA phosphorylation through affecting HogA-P upstream kinases.
Timely septation and conidiation are essential for fungal asexual reproduction . Here , we identified a putative dual-specificity tyrosine phosphorylation-regulated kinase PomA , as a suppressor of a conserved SepH ( Cdc7p ) kinase in the septation initiation network ( SIN ) cascade , is a new identified negative regulator for septation and conidiation in A . nidulans . Our findings indicated that reversible protein phosphorylation of the high-osmolarity glycerol gene hogA regulated by the SIN-SepH-PomA kinase cascade plays a key role for fungal cell septation and asexual reproduction . However , when fungi meet osmostress , they bypass the originally required SIN protein cascade to fit the environmental niches by increasing the phosphorylation of HogA .