The nuclear Dbf2-related kinase COT1 and the mitogen-activated protein kinases MAK1 and MAK2 genetically interact to regulate filamentous growth, hyphal fusion and sexual development in Neurospora crassa

Genetics. 2008 Jul;179(3):1313-25. doi: 10.1534/genetics.108.089425. Epub 2008 Jun 18.


Ndr kinases, such as Neurospora crassa COT1, are important for cell differentiation and polar morphogenesis, yet their input signals as well as their integration into a cellular signaling context are still elusive. Here, we identify the cot-1 suppressor gul-4 as mak-2 and show that mutants of the gul-4/mak-2 mitogen-activated protein (MAP) kinase pathway suppress cot-1 phenotypes along with a concomitant reduction in protein kinase A (PKA) activity. Furthermore, mak-2 pathway defects are partially overcome in a cot-1 background and are associated with increased MAK1 MAPK signaling. A comparative characterization of N. crassa MAPKs revealed that they act as three distinct modules during vegetative growth and asexual development. In addition, common functions of MAK1 and MAK2 signaling during maintenance of cell-wall integrity distinguished the two ERK-type pathways from the p38-type OS2 osmosensing pathway. In contrast to separate functions during vegetative growth, the concerted activity of the three MAPK pathways is essential for cell fusion and for the subsequent formation of multicellular structures that are required for sexual development. Taken together, our data indicate a functional link between COT1 and MAPK signaling in regulating filamentous growth, hyphal fusion, and sexual development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / enzymology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Fungal Proteins / metabolism*
  • Gene Deletion
  • Histidine Kinase
  • Hyphae / cytology
  • Hyphae / enzymology*
  • Hyphae / growth & development
  • Models, Biological
  • Neurospora crassa / cytology
  • Neurospora crassa / enzymology*
  • Neurospora crassa / growth & development*
  • Phenotype
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Cell Cycle Proteins
  • Fungal Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • DBF2 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Histidine Kinase