Cla4 kinase triggers destruction of the Rac1-GEF Cdc24 during polarized growth inUstilago maydis

Abstract

In the dimorphic fungus Ustilago maydis, Rac1 and its activator Cdc24 are essential for hyphal tip growth. Rac1 is shown to stimulate Cla4 kinase, which in turn triggers destruction of Cdc24. Expression of stabilized Cdc24 interferes with cell polarization, indicating that negative feedback regulation of Cdc24 is critical for tip growth.

CDC-42 and RAC-1 regulate opposite chemotropisms inNeurospora crassa

“…When considered together, these data indicate that repositioning of activated RAC-1 is probably relayed to MAK-2 via CLA-4. This is consistent with previous work indicating that two separate but complementary GTPase and PAK signaling modules operate in fungi (Li et al, 2004;Mahlert et al, 2006;Rolke and Tudzynski, 2008;Frieser et al, 2011). Recently, BEM-1 has been identified as the likely scaffolding protein for the assembly of a plasma membrane-associated signaling complex capable of interacting with the NRC-1-MEK-2-MAK-2 kinase module during cell fusion (Schürg et al, 2012).…”

“…These dual-use properties of HYM-1 have been linked to phosphorylation of MAK-2 and the physical interaction with both PAKs, STE-20 and CLA-4 (Dettmann et al, 2012). A ternary Bem1-Rac1-Cla4 complex has also recently been identified to regulate switching between isotropic and polarized growth in Ustilago maydis (Frieser et al, 2011).…”

Small-GTPase-Associated Signaling by the Guanine Nucleotide Exchange Factors CpDock180 and CpCdc24, the GTPase Effector CpSte20, and the Scaffold Protein CpBem1 in Claviceps purpurea

“…In addition to this, CpSte20 is able to interact with CpCdc24, which could represent a feedback loop of a GTPase effector on a GTPase regulator. The association of both CpSte20 and CpCdc24 underlines this suggestion, as a Bem1-mediated negative-feedback loop of Cla4 on Cdc24 has been postulated for S. cerevisiae and U. maydis (36,40,41), which could also apply for the CpSte20-CpCdc24 system. However, positive effects on GEF activity of the formation of ternary GEF-GTPase-effector complexes have been suggested for mammalian systems (44).…”

“…The ability of CpBem1 to interact with CpRac has its analogue in the interaction of Cdc42 and Bem1 homologues in S. cerevisiae, S. pombe, and C. albicans (36,(76)(77)(78). In higher fungi, this affinity for Bem1 homologues is presumably taken over by Rac homologues as in U. maydis (41). The role of CpCla4 as an effector of active CpRac has been shown before (15) and has now been confirmed by coimmunoprecipitation.…”

“…In S. cerevisiae and U. maydis, the PAK Cla4 is part of the Bem1-Cdc24-Cdc42 complex and is probably involved in feedback regulations of GEFs and GTPases (36,40,41). The importance of Cla4 kinase signaling appears to be more important in higher fungi, while in yeasts the closely related PAK Ste20 fulfils a more crucial role (10,(42)(43)(44)(45)(46).…”