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Eukaryotic Cell, September 2008, p. 1530-1539, Vol. 7, No. 9
1535-9778/08/$08.00+0     doi:10.1128/EC.00080-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Aspergillus fumigatus RasA Regulates Asexual Development and Cell Wall Integrity

Jarrod R. Fortwendel, Kevin K. Fuller, Timothy J. Stephens, W. Clark Bacon, David S. Askew, and Judith C. Rhodes^*

Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Way, Cincinnati, Ohio 45267-0529

Received 3 March 2008/ Accepted 11 June 2008

The Ras family of proteins is a large group of monomeric GTPases. Members of the fungal Ras family act as molecular switches that transduce signals from the outside of the cell to signaling cascades inside the cell. A. fumigatus RasA is 94% identical to the essential RasA gene of Aspergillus nidulans and is the Ras family member sharing the highest identity to Ras homologs studied in many other fungi. In this study, we report that rasA is not essential in A. fumigatus, but its absence is associated with slowed germination and a severe defect in radial growth. The rasA hyphae were more than two times the diameter of wild-type hyphae, and they displayed repeated changes in the axis of polarity during hyphal growth. The deformed hyphae accumulated numerous nuclei within each hyphal compartment. The rasA mutant conidiated poorly, but this phenotype could be ameliorated by growth on osmotically stabilized media. The rasA mutant also showed increased susceptibility to cell wall stressors, stained more intensely with calcofluor white, and was refractory to lysing enzymes used to make protoplasts, suggesting an alteration of the cell wall. All phenotypes associated with deletion of rasA could be corrected by reinsertion of the wild-type gene. These data demonstrate a crucial role for RasA in both hyphal growth and asexual development in A. fumigatus and provide evidence that RasA function is linked to cell wall integrity.

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* Corresponding author. Mailing address: Department of Pathology, University of Cincinnati, P.O. Box 670529, Cincinnati, OH 45267-0529. Phone: (513) 558-0130. Fax: (513) 558-2141. E-mail: Judith.rhodes{at}uc.edu

Published ahead of print on 7 July 2008.

Present address: Department of Pediatrics, Duke University Medical Center, Research Drive, Durham, NC 27710.

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Eukaryotic Cell, September 2008, p. 1530-1539, Vol. 7, No. 9
1535-9778/08/$08.00+0     doi:10.1128/EC.00080-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

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• Fortwendel, J. R., Juvvadi, P. R., Pinchai, N., Perfect, B. Z., Alspaugh, J. A., Perfect, J. R., Steinbach, W. J. (2009). Differential Effects of Inhibiting Chitin and 1,3-{beta}-D-Glucan Synthesis in Ras and Calcineurin Mutants of Aspergillus fumigatus. Antimicrob. Agents Chemother. 53: 476-482 [Abstract] [Full Text]