Academic journal article Genetics

A Non-Mendelian MAPK-Generated Hereditary Unit Controlled by a Second MAPK Pathway in Podospora Anserina

Academic journal article Genetics

A Non-Mendelian MAPK-Generated Hereditary Unit Controlled by a Second MAPK Pathway in Podospora Anserina

Article excerpt

ABSTRACT The Podospora anserina PaMpk1 MAP kinase (MAPK) signaling pathway can generate a cytoplasmic and infectious element resembling prions. When present in the cells, this C element causes the crippled growth (CG) cell degeneration. CG results from the inappropriate autocatalytic activation of the PaMpk1 MAPK pathway during growth, whereas this cascade normally signals stationary phase. Little is known about the control of such prion-like hereditary units involved in regulatory inheritance. Here, we show that another MAPK pathway, PaMpk2, is crucial at every stage of the fungus life cycle, in particular those controlled by PaMpk1 during stationary phase, which includes the generation of C. Inactivation of the third P. anserina MAPK pathway, PaMpk3, has no effect on the development of the fungus. Mutants of MAPK, MAPK kinase, and MAPK kinase kinase of the PaMpk2 pathway are unable to present CG. This inability likely relies upon an incorrect activation of PaMpk1, although this MAPK is normally phosphorylated in the mutants. In PaMpk2 null mutants, hyphae are abnormal and PaMpk1 is mislocalized. Correspondingly, stationary phase differentiations controlled by PaMpk1 are defective in the mutants of the PaMpk2 cascade. Constitutive activation of the PaMpk2 pathway mimics in many ways its inactivation, including an effect on PaMpk1 localization. Analysis of double and triple mutants inactivated for two or all three MAPK genes undercover new growth and differentiation phenotypes, suggesting overlapping roles. Our data underscore the complex regulation of a prion-like element in a model organism.

MAP kinase (MAPK) modules are signaling devices used by all eukaryotes to signal various developmental programs or to respond to environmental stresses (Widmann et al. 1999). They are composed of three kinases that sequentially phosphorylate their targets: a MAPKKK that phosphorylates one or several MAPKK(s), which in turn phosphorylate(s) one or several MAPK(s). These latter kinases phosphorylate various cellular components, especially transcription factors, resulting in gene expression modification (Garrington and Johnson 1999). These MAPK modules are embedded in more complex regulatory networks, including other MAPK pathways (Saito 2010), whose complexity is known to generate emergent properties that rule cellular behavior (Neves and Iyengar 2002; Ferrell et al. 2009). This includes bistability, memory, hysteresis, and threshold responses. In some instances, the alternate states adopted by the cells are so stable that they can be transmitted through cell divisions, as exemplified by the crippled growth (CG) degeneration of the filamentous fungus Podospora anserina (reviewed in Lalucque et al. 2010). This kind of regulatory inheritance is now suspected of playing an important role in various physiological processes, including tumor formation, cell differentiation, and degeneration (Blagosklonny 2005; Lalucque et al. 2010), yet it is still poorly studied.

In filamentous fungi, MAPKs are mostly studied for their involvement in the infectious process of plant pathogenic species (reviewed in Zhao et al. 2007) and in model saprobes such as Aspergillus nidulans (Bussink and Osmani 1999; Kawasaki et al. 2002) and Neurospora crassa (Maerz et al. 2008; Fleissner et al. 2009) or in the human pathogen A. fumigatus (May et al. 2005). Through complete genome sequence analyses, three MAPK pathways have been characterized in most filamentous ascomycetes (Zhao et al. 2007; Rispail et al. 2009). One is orthologous to the MPK1 pathway involved in the control of the cell wall integrity in Saccharomyces cerevisiae, the other to the FUS3 pathway involved in the control of cell fusion during sexual reproduction, and the third one to the HOG1 pathway regulating the response to high osmolarity. Unlike yeasts, in which many connections between the MAPK pathways have been described, little is known about the entire MAPK network and potential cross-talks in filamentous fungi. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.