PRO40 Is a Scaffold Protein of the Cell Wall Integrity Pathway, Linking the MAP Kinase Module to the Upstream Activator Protein Kinase C
The specific response to environmental cues is crucial for cell differentiation and is often mediated by highly conserved eukaryotic MAP kinase (MAPK) pathways. How these pathways react specifically to huge numbers of different cues is still unclear, and current literature about adapter and scaffolding proteins remains scarce. However, gaining fundamental insight into molecular signaling determinants is pivotal for combating diseases with impaired signal transduction processes, such as Alzheimer's disease or cancer. Importantly, signal transduction can easily be studied in lower eukaryotes like filamentous fungi that are readily genetically tractable. The fungus Sordaria macrospora has a long history as an ideal model system for cell differentiation, and we show here that the proposed cell wall integrity (CWI) MAPK module of this fungus controls differentiation of sexual fruiting bodies, cell fusion, polar growth and cell wall stress response. We further discovered that developmental protein PRO40 binds the MAPK kinase kinase (MAPKKK), the MAPK kinase (MAPKK) and upstream activator protein kinase C (PKC1) of the CWI pathway and is required for MAK1 activity, thereby providing evidence that PRO40 is a scaffold protein. Collectively, our findings reveal a molecular role for a protein implicated in development, cell fusion, symbiosis, and pathogenicity in different fungi.
Vyšlo v časopise:
PRO40 Is a Scaffold Protein of the Cell Wall Integrity Pathway, Linking the MAP Kinase Module to the Upstream Activator Protein Kinase C. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004582
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004582
Souhrn
The specific response to environmental cues is crucial for cell differentiation and is often mediated by highly conserved eukaryotic MAP kinase (MAPK) pathways. How these pathways react specifically to huge numbers of different cues is still unclear, and current literature about adapter and scaffolding proteins remains scarce. However, gaining fundamental insight into molecular signaling determinants is pivotal for combating diseases with impaired signal transduction processes, such as Alzheimer's disease or cancer. Importantly, signal transduction can easily be studied in lower eukaryotes like filamentous fungi that are readily genetically tractable. The fungus Sordaria macrospora has a long history as an ideal model system for cell differentiation, and we show here that the proposed cell wall integrity (CWI) MAPK module of this fungus controls differentiation of sexual fruiting bodies, cell fusion, polar growth and cell wall stress response. We further discovered that developmental protein PRO40 binds the MAPK kinase kinase (MAPKKK), the MAPK kinase (MAPKK) and upstream activator protein kinase C (PKC1) of the CWI pathway and is required for MAK1 activity, thereby providing evidence that PRO40 is a scaffold protein. Collectively, our findings reveal a molecular role for a protein implicated in development, cell fusion, symbiosis, and pathogenicity in different fungi.
Zdroje
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
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