Proper actin ring formation and septum constriction requires coordinated regulation of SIN and MOR pathways through the germinal centre kinase MST-1.
Nuclear DBF2p-related (NDR) kinases constitute a functionally conserved protein family of eukaryotic regulators that control cell division and polarity. In fungi, they function as effector kinases of the morphogenesis (MOR) and septation initiation (SIN) networks and are activated by pathway-specific germinal centre (GC) kinases. We characterized a third GC kinase, MST-1, that connects both kinase cascades. Genetic and biochemical interactions with SIN components and life cell imaging identify MST-1 as SIN-associated kinase that functions in parallel with the GC kinase SID-1 to activate the SIN-effector kinase DBF-2. SID-1 and MST-1 are both regulated by the upstream SIN kinase CDC-7, yet in an opposite manner. Aberrant cortical actomyosin rings are formed in Δmst-1, which resulted in mis-positioned septa and irregular spirals, indicating that MST-1-dependent regulation of the SIN is required for proper formation and constriction of the septal actomyosin ring. However, MST-1 also interacts with several components of the MOR network and modulates MOR activity at multiple levels. MST-1 functions as promiscuous enzyme and also activates the MOR effector kinase COT-1 through hydrophobic motif phosphorylation. In addition, MST-1 physically interacts with the MOR kinase POD-6, and dimerization of both proteins inactivates the GC kinase hetero-complex. These data specify an antagonistic relationship between the SIN and MOR during septum formation in the filamentous ascomycete model Neurospora crassa that is, at least in part, coordinated through the GC kinase MST-1. The similarity of the SIN and MOR pathways to the animal Hippo and Ndr pathways, respectively, suggests that intensive cross-communication between distinct NDR kinase modules may also be relevant for the homologous NDR kinases of higher eukaryotes.
Institute for Biology II - Molecular Plant Physiology, Albert-Ludwigs University Freiburg, Freiburg, Germany.
Yvonne
Y
Heilig
Institute for Biology II - Molecular Plant Physiology, Albert-Ludwigs University Freiburg, Freiburg, Germany.
Anne
A
Dettmann
Department of Microbiology, Center for Scientific Research and Higher Education of Ensenada (CICESE), Baja California, Mexico.
Rosa R
RR
Mouriño-Pérez
Institute for Microbiology and Genetics, University of Goettingen, Goettingen, Germany.
Kerstin
K
Schmitt
Institute for Microbiology and Genetics, University of Goettingen, Goettingen, Germany.
Oliver
O
Valerius
Institute for Biology II - Molecular Plant Physiology, Albert-Ludwigs University Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), Albert-Ludwigs University Freiburg, Freiburg, Germany.
Stephan
S
Seiler
D000199:Actins / Q000235:genetics*; D000205:Actomyosin / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division; D005656:Fungal Proteins / Q000235:genetics; D000081410:Germinal Center Kinases; D026901:Membrane Transport Proteins / Q000235:genetics; D009024:Morphogenesis / Q000235:genetics*; D009492:Neurospora crassa / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
D000199:Actins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D000081410:Germinal Center Kinases; D026901:Membrane Transport Proteins; D000205:Actomyosin; D017346:Protein Serine-Threonine Kinases