The small GTPase Ras1 regulates several processes in Candida albicans, including the switch from the yeast to the filamentous, hyphal form. This transition is thought to be triggered by a spike in cyclic AMP levels that is generated following interaction of the adenylate cyclase Cyr1 with the active (GTP-bound), plasma membrane-associated form of Ras1. Here, the authors identify a proteolysis-dependent mechanism that controls Ras1 signalling and, thus, filamentation in C. albicans. Plasma membrane-associated Ras1 was found to be cleaved at the carboxy-terminal hypervariable region, inhibiting the interaction of Ras1 with Cyr1 and downregulating Ras1-dependent cAMP signalling and, consequently, hyphal growth. Notably, Ras1 cleavage was regulated by cAMP signalling, as the levels of cleaved Ras1 decreased in response to high levels of cAMP but increased in the presence of the quorum sensing molecule farnesol (which inhibits Cyr1 function).
References
Piispanen, A. et al. Regulated proteolysis of Candida albicans Ras1 is involved in morphogenesis and quorum sensing regulation. Mol. Microbiol. 21 May 2013 (10.1111/mmi.12268)
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David, R. Ras1 as a switch for Candida albicans. Nat Rev Microbiol 11, 431 (2013). https://doi.org/10.1038/nrmicro3061
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DOI: https://doi.org/10.1038/nrmicro3061