A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast.
A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast.
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DOI：
10.1038/s41598-017-06001-9
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发表时间：
2017-07-18
影响因子：
4.6
通讯作者：
Arroyo J
中科院分区：
文献类型：
--
作者：
García R;Bravo E;Diez-Muñiz S;Nombela C;Rodríguez-Peña JM;Arroyo J
真菌细胞触发适应性机制，在破坏细胞壁完整性的情况下生存。我们在这里表明，caspofungin抑制β-1,3-葡聚糖合成所引发的全球转录反应，包括一组依赖于Slt2的基因，细胞壁完整性（CWI）途径的MAPK，以及一组独立于Slt2调节的基因。环AMP/蛋白激酶A （PKA）信号通路负调控的基因在后一组中被过量表达。此外，通过抑制β-1,3-葡聚糖合成介导的细胞壁应激，而不是通过其他细胞壁干扰化合物介导的细胞壁应激，负调控PKA信号传导，如Msn2的核定位、细胞糖原积累、细胞内cAMP水平的降低以及小GTPase Ras2的激活和PKA已知底物磷酸化的严重降低。所有这些作用都依赖于CWI通路的质膜传感器Wsc1。此外，caspofungin诱导胞质pH降低，这取决于Wsc1的细胞外区域。因此，真菌细胞壁中β-1,3-葡聚糖网络的改变，通过Wsc1诱导CWI通路的激活和PKA信号的平行抑制。
Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway, and a broad group of genes regulated independently of Slt2. Genes negatively regulated by the cyclic AMP/Protein Kinase A (PKA) signaling pathway were overrepresented in the latter group. Moreover, cell wall stress mediated by inhibition of β-1,3-glucan synthesis, but not by other cell wall interfering compounds, negatively regulated PKA signaling as indicated by the nuclear localisation of Msn2, cellular glycogen accumulation, a decrease of intracellular cAMP levels and a severe decrease in both the activation of the small GTPase Ras2 and the phosphorylation of known substrates of PKA. All these effects relied on the plasma membrane-spanning sensor of the CWI pathway Wsc1. In addition, caspofungin induced a reduction in the cytosolic pH, which was dependent on the extracellular region of Wsc1. Therefore, alterations of the β-1,3-glucan network in the fungal cell wall, induce, through Wsc1, the activation of the CWI pathway and parallel inhibition of PKA signaling.
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影响因子：
11.3
作者：
Conrad M;Schothorst J;Kankipati HN;Van Zeebroeck G;Rubio-Texeira M;Thevelein JM
通讯作者：
Thevelein JM
影响因子：
7
作者：
Carter, GW;Rupp, S;Galitski, T
通讯作者：
Galitski, T
影响因子：
2.1
作者：
Dechant, Reinhard;Peter, Matthias
通讯作者：
Peter, Matthias
影响因子：
3.3
作者：
Bermejo, Clara;Rodriguez, Estefania;Arroyo, Javier
通讯作者：
Arroyo, Javier
影响因子：
3.3
作者：
Causton, HC;Ren, B;Young, RA
通讯作者：
Young, RA