title: The NDR kinase scaffold HYM1/MO25 is essential for MAK2 map kinase signaling in Neurospora crassa.
abstract: Cell communication is essential for eukaryotic development, but our knowledge of molecules and mechanisms required for intercellular communication is fragmentary. In particular, the connection between signal sensing and regulation of cell polarity is poorly understood. In the filamentous ascomycete Neurospora crassa, germinating spores mutually attract each other and subsequently fuse. During these tropic interactions, the two communicating cells rapidly alternate between two different physiological states, probably associated with signal delivery and response. The MAK2 MAP kinase cascade mediates cell-cell signaling. Here, we show that the conserved scaffolding protein HYM1/MO25 controls the cell shape-regulating NDR kinase module as well as the signal-receiving MAP kinase cascade. HYM1 functions as an integral part of the COT1 NDR kinase complex to regulate the interaction with its upstream kinase POD6 and thereby COT1 activity. In addition, HYM1 interacts with NRC1, MEK2, and MAK2, the three kinases of the MAK2 MAP kinase cascade, and co-localizes with MAK2 at the apex of growing cells. During cell fusion, the three kinases of the MAP kinase module as well as HYM1 are recruited to the point of cell-cell contact. hym-1 mutants phenocopy all defects observed for MAK2 pathway mutants by abolishing MAK2 activity. An NRC1-MEK2 fusion protein reconstitutes MAK2 signaling in hym-1, while constitutive activation of NRC1 and MEK2 does not. These data identify HYM1 as a novel regulator of the NRC1-MEK2-MAK2 pathway, which may coordinate NDR and MAP kinase signaling during cell polarity and intercellular communication.
authors.affiliation: Institute for Microbiology and Genetics, University of Goettingen, Goettingen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Dettmann
authors.forename: Julia
authors.initials: J
authors.lastname: Illgen
authors.forename: Sabine
authors.initials: S
authors.lastname: März
authors.forename: Timo
authors.initials: T
authors.lastname: Schürg
authors.forename: Andre
authors.initials: A
authors.lastname: Fleissner
authors.forename: Stephan
authors.initials: S
authors.lastname: Seiler
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D016764:Cell Polarity; D048430:Cell Shape; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D000071677:Histidine Kinase; D020935:MAP Kinase Signaling System; D009492:Neurospora crassa / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D013170:Spores / Q000235:genetics / Q000254:growth & development / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000071677:Histidine Kinase