EC Accepts, published online ahead of print on 5 June 2009

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Eukaryotic Cell doi:10.1128/EC.00006-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Role of the Cell Wall Integrity and FG MAPK Pathways in Cell Wall Remodeling During Filamentous Growth

Barbara Birkaya, Abraham Maddi, Jyoti Joshi, Stephen J. Free, and Paul J. Cullen^*

Department of Biological Sciences, SUNY-Buffalo, Amherst NY 14260-1300

^* To whom correspondence should be addressed. Email: pjcullen{at}buffalo.edu.

Many fungal species including pathogens exhibit filamentous growth as a means of foraging for nutrients. Genetic screens were performed to identify genes required for filamentous growth in the budding yeast Saccharomyces cerevisiae. Genes encoding proteins with established functions in transcriptional activation (MCM1, MAT2, PHD1, MSN2, SIR4, and HMS2), cell wall integrity (MPT5, WSC2, and MID2), and cell polarity (BUD5) were identified as potential regulators of filamentous growth. The transcription factors MCM1 and MAT2 induced invasive growth by promoting diploid-specific bipolar budding in haploid cells. Components of the cell wall integrity pathway including the cell-surface proteins Slg1p/Wsc1p, Wsc2p, Mid2p, and the MAPK Slt2p/Mpk1p contributed to multiple aspects of the filamentous growth response including cell elongation, cell-cell adherence, and agar invasion. Mid2p and Wsc2p stimulated the filamentous growth MAPK (FG) pathway through the signaling mucin Msb2p and components of the MAPK cascade. The FG pathway contributed to cell wall integrity in parallel with the cell wall integrity pathway and in opposition with the high osmolarity glycerol response (HOG) pathway. MASS SPEC approaches identified components of the filamentous cell wall including the mucin-like proteins Msb2p, Flo11p, and subtelomeric (silenced) mucin Flo10p. Secretion of Msb2p, which occurs as part of the maturation of the protein, was inhibited by the ß-1,3-glucan layer of the cell wall, which highlights a new regulatory aspect to cell wall remodeling in this organism. Disruption of ß-1,3-glucan linkages induced mucin shedding and resulted in defects in cell-cell adhesion and invasion of cells into the agar matrix.

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