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Eukaryotic Cell, June 2004, p. 741-751, Vol. 3, No. 3
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.3.741-751.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Candida albicans Rim13p, a Protease Required for Rim101p Processing at Acidic and Alkaline pHs

Mingchun Li,1 Samuel J. Martin,1 Vincent M. Bruno,2 Aaron P. Mitchell,2 and Dana A. Davis1*

Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455,1 Department of Microbiology and Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, New York, New York 100322

Received 1 December 2003/ Accepted 9 April 2004

Candida albicans is an important commensal of mucosal surfaces that is also an opportunistic pathogen. This organism colonizes a wide range of host sites that differ in pH; thus, it must respond appropriately to this environmental stress to survive. The ability to respond to neutral-to-alkaline pHs is governed in part by the RIM101 signal transduction pathway. Here we describe the analysis of C. albicans Rim13p, a homolog of the Rim13p/PalB calpain-like protease member of the RIM101/pacC pathway from Saccharomyces cerevisiae and Aspergillus nidulans, respectively. RIM13, like other members of the RIM101 pathway, is required for alkaline pH-induced filamentation and growth under extreme alkaline conditions. Further, our studies suggest that the RIM101 pathway promotes pH-independent responses, including resistance to high concentrations of lithium and to the drug hygromycin B. RIM13 encodes a calpain-like protease, and we found that Rim101p undergoes a Rim13p-dependent C-terminal proteolytic processing event at neutral-to-alkaline pHs, similar to that reported for S. cerevisiae Rim101p and A. nidulans PacC. However, we present evidence that suggests that C. albicans Rim101p undergoes a novel processing event at acidic pHs that has not been reported in either S. cerevisiae or A. nidulans. Thus, our results provide a framework to understand how the C. albicans Rim101p processing pathway promotes alkaline pH-independent processes.

* Corresponding author. Mailing address: 1360 Mayo Building MMC196, 420 Delaware St., Dept. of Microbiology, University of Minnesota, Minneapolis MN 55455. Phone: (612) 624-1912. Fax: (612) 626-0623. E-mail: dadavis{at}umn.edu.

Eukaryotic Cell, June 2004, p. 741-751, Vol. 3, No. 3
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.3.741-751.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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Copyright © 2004 by the American Society for Microbiology.