HAM-5 functions as a MAP kinase scaffold during cell fusion in Neurospora crassa

PLoS Genet. 2014 Nov 20;10(11):e1004783. doi: 10.1371/journal.pgen.1004783. eCollection 2014 Nov.

Abstract

Cell fusion in genetically identical Neurospora crassa germlings and in hyphae is a highly regulated process involving the activation of a conserved MAP kinase cascade that includes NRC-1, MEK-2 and MAK-2. During chemotrophic growth in germlings, the MAP kinase cascade members localize to conidial anastomosis tube (CAT) tips every ∼8 minutes, perfectly out of phase with another protein that is recruited to the tip: SOFT, a recently identified scaffold for the MAK-1 MAP kinase pathway in Sordaria macrospora. How the MAK-2 oscillation process is initiated, maintained and what proteins regulate the MAP kinase cascade is currently unclear. A global phosphoproteomics approach using an allele of mak-2 (mak-2Q100G) that can be specifically inhibited by the ATP analog 1NM-PP1 was utilized to identify MAK-2 kinase targets in germlings that were potentially involved in this process. One such putative target was HAM-5, a protein of unknown biochemical function. Previously, Δham-5 mutants were shown to be deficient for hyphal fusion. Here we show that HAM-5-GFP co-localized with NRC-1, MEK-2 and MAK-2 and oscillated with identical dynamics from the cytoplasm to CAT tips during chemotropic interactions. In the Δmak-2 strain, HAM-5-GFP localized to punctate complexes that did not oscillate, but still localized to the germling tip, suggesting that MAK-2 activity influences HAM-5 function/localization. However, MAK-2-GFP showed cytoplasmic and nuclear localization in a Δham-5 strain and did not localize to puncta. Via co-immunoprecipitation experiments, HAM-5 was shown to physically interact with NRC-1, MEK-2 and MAK-2, suggesting that it functions as a scaffold/transport hub for the MAP kinase cascade members for oscillation and chemotropic interactions during germling and hyphal fusion in N. crassa. The identification of HAM-5 as a scaffold-like protein will help to link the activation of MAK-2 cascade to upstream factors and proteins involved in this intriguing process of fungal communication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Fusion
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Histidine Kinase
  • Hyphae / genetics
  • Hyphae / growth & development
  • MAP Kinase Kinase 2 / genetics*
  • MAP Kinase Kinase 2 / metabolism
  • MAP Kinase Signaling System / genetics
  • Membrane Proteins / genetics*
  • Mitogen-Activated Protein Kinases / genetics*
  • Neurospora crassa / genetics
  • Neurospora crassa / metabolism
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Spores, Fungal / genetics
  • Spores, Fungal / growth & development

Substances

  • Fungal Proteins
  • Membrane Proteins
  • Protein Kinases
  • nrc-1 protein, Neurospora crassa
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 2
  • Histidine Kinase