Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

2015 ◽  
Vol 458 (4) ◽  
pp. 802-809 ◽  
Author(s):  
Yuta Tsukamoto ◽  
Satoshi Kagiwada ◽  
Sayuri Shimazu ◽  
Kaoru Takegawa ◽  
Tetsuko Noguchi ◽  
...  
2014 ◽  
Vol 13 (4) ◽  
pp. 470-482 ◽  
Author(s):  
Andrea Herrmann ◽  
Britta A. M. Tillmann ◽  
Janine Schürmann ◽  
Michael Bölker ◽  
Paul Tudzynski

ABSTRACTMonomeric GTPases of the Rho subfamily are important mediators of polar growth and NADPH (Nox) signaling in a variety of organisms. These pathways influence the ability ofClaviceps purpureato infect host plants. GTPase regulators contribute to the nucleotide loading cycle that is essential for proper functionality of the GTPases. Scaffold proteins gather GTPase complexes to facilitate proper function. The guanine nucleotide exchange factors (GEFs) CpCdc24 and CpDock180 activate GTPase signaling by triggering nucleotide exchange of the GTPases. Here we show that CpCdc24 harbors nucleotide exchange activity for both Rac and Cdc42 homologues. The GEFs partly share the cellular distribution of the GTPases and interact with the putative upstream GTPase CpRas1. Interaction studies show the formation of higher-order protein complexes, mediated by the scaffold protein CpBem1. Besides the GTPases and GEFs, these complexes also contain the GTPase effectors CpSte20 and CpCla4, as well as the regulatory protein CpNoxR. Functional characterizations suggest a role of CpCdc24 mainly in polarity, whereas CpDock180 is involved in stress tolerance mechanisms. These findings indicate the dynamic formation of small GTPase complexes and improve the model for GTPase-associated signaling inC. purpurea.


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