Originally published as Genetics Published Articles Ahead of Print on June 18, 2008.

Genetics, Vol. 179, 1313-1325, July 2008, Copyright © 2008
doi:10.1534/genetics.108.089425

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

Sabine Maerz*, Carmit Ziv{dagger}, Nico Vogt*,{ddagger}, Kerstin Helmstaedt*,{ddagger}, Nourit Cohen{dagger}, Rena Gorovits{dagger}, Oded Yarden{dagger} and Stephan Seiler*,{ddagger},1

* Institut für Mikrobiologie und Genetik Abteilung Molekulare Mikrobiologie, {ddagger} DFG Research Center of Molecular Physiology of the Brain (CMPB), Universität Göttingen, D-37077 Göttingen, Germany and {dagger} Department of Plant Pathology and Microbiology, The Otto Warburg Minerva Center for Agricultural Biotechnology, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel

1 Corresponding author: Universität Göttingen, Grisebachstrasse 8, D-37077 Göttingen, Germany.
E-mail: sseiler{at}gwdg.de

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.