EC Accepts, published online ahead of print on 19 June 2009
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Eukaryotic Cell doi:10.1128/EC.00081-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Msb2 signaling mucin controls the activation of the Cek1 MAP kinase in Candida albicans

Elvira Román, Fabien Cottier, Joachim F. Ernst, and Jesús Pla*

Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain; Institut für Mikrobiologie, Heinrich-Heine-Universitaet Düsseldorf, Universitaetsstr. 1/26.12, 40225 Düesseldorf, Germany

* To whom correspondence should be addressed. Email: jesuspla{at}farm.ucm.es.


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Abstract

We have characterized the role that the Msb2 protein plays in the fungal pathogen Candida albicans using mutants defective in the putative upstream components of the HOG pathway. Msb2, in cooperation with Sho1, controls the activation of the Cek1 MAP kinase under conditions that damage the cell wall thus defining Msb2 as a signaling element of this pathway in this fungus. msb2 mutants display altered sensitivity to Congo red, caspofungin, zymolyase or tunicamycin indicating that this protein is involved in cell wall biogenesis. Msb2 (as well as Sho1 and Hst7) is involved in the transmission of the signal towards Cek1 mediated by the Cdc42 GTPase, as revealed by the use of activated alleles (Cdc42G12V) of this protein. msb2 mutants have stronger defective invasion phenotypes on defined solid media that use mannitol or sucrose as carbon sources (as well as under hypoxia) compared to sho1. Interestingly, Msb2 contributes to growth under high osmolarity when both branches of the HOG pathway are altered as triple ssk1 msb2 sho1 mutants (but not any single or double mutant) are osmosensitive. However, this is independent of Hog1 as neither Hog1 phosphorylation nor Hog1 translocation to the nucleus nor glycerol accumulation is affected in this mutant following an osmotic shock. These results reveal essential functions in morphogenesis, invasion, cell wall biogenesis and growth under high osmolarity for Msb2 in Candida albicans and suggest the divergence/specialization of this signaling pathway in filamentous fungi.