The Aspergillus nidulans MAPK Module AnSte11-Ste50-Ste7-Fus3 Controls Development and Secondary Metabolism

Abstract

The sexual Fus3 MAP kinase module of yeast is highly conserved in eukaryotes and transmits external signals from the plasma membrane to the nucleus. We show here that the module of the filamentous fungus Aspergillus nidulans (An) consists of the AnFus3 MAP kinase, the upstream kinases AnSte7 and AnSte11, and the AnSte50 adaptor. The fungal MAPK module controls the coordination of fungal development and secondary metabolite production. It lacks the membrane docking yeast Ste5 scaffold homolog; but, similar to yeast, the entire MAPK module's proteins interact with each other at the plasma membrane. AnFus3 is the only subunit with the potential to enter the nucleus from the nuclear envelope. AnFus3 interacts with the conserved nuclear transcription factor AnSte12 to initiate sexual development and phosphorylates VeA, which is a major regulatory protein required for sexual development and coordinated secondary metabolite production. Our data suggest that not only Fus3, but even the entire MAPK module complex of four physically interacting proteins, can migrate from plasma membrane to nuclear envelope.

Author Summary

Mitogen activated protein (MAP) kinase cascades are conserved from yeast to man to transmit an external signal to the nucleus and induce an appropriate cellular response. The yeast Fus3 MAP kinase module represents a textbook paradigm for signal transduction. The pathway is activated by external sexual hormones triggering several kinases that transmit the signal at the plasma membrane to Fus3. Phosphorylated Fus3 is released from the membrane-associated module, crosses the cytoplasm, and enters the nucleus to activate transcription factors for sexual development. We describe here the Fus3 MAPK pathway of a filamentous fungus that controls sexual development as well as secondary metabolism, which are coordinated processes in filamentous fungi. Aspergillus nidulans is able to release Fus3 as a complex from the membrane. Complexes of Fus3 can include two additional kinases and an adaptor protein, and these complexes can migrate from the membrane to the nuclear envelope where only A. nidulans Fus3 can enter the nucleus to control nuclear regulators. Revealing specific functions of cellular Aspergillus Fus3 complexes in signal transduction to control fungal development and secondary metabolism will be a fascinating future task.