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MBC in Press, published online ahead of print May 11, 2005
Mol. Biol. Cell 10.1091/mbc.E04-12-1081

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Submitted on December 14, 2004
Revised on April 28, 2005
Accepted on May 3, 2005

The Mitotic Cyclins Clb2p and Clb4p Affect Morphogenesis in Candida albicans

Eric S. Bensen,*{dagger} Andres Clemente-Blanco,{ddagger} Kenneth R. Finley,* Jaime Correa-Bordes,{ddagger} and Judith Berman*{sect}

Departments of *Genetics, Cell Biology, and Development and {sect}Microbiology, University of Minnesota, Minneapolis, MN 55455; {ddagger}Departamento de Microbiología, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain

Monitoring Editor: Mark Solomon

The ability of Candida albicans to switch cellular morphologies is crucial for its ability to cause infection. Because the cell cycle machinery participates in S. cerevisiae filamentous growth, we characterized in detail the two C. albicans B-type cyclins, CLB2 and CLB4, to better understand the molecular mechanisms that underlie the C. albicans morphogenic switch. Both Clb2p and Clb4p levels are cell cycle regulated, peaking at G2/M and declining before mitotic exit. On hyphal induction, the accumulation of the G1 cyclin Cln1p was prolonged while the accumulation of both Clb proteins was delayed when compared with yeast form cells, indicating that CLB2 and CLB4 are differentially regulated in the two morphologies and that the dynamics of cyclin appearance differs between yeast and hyphal forms of growth. Clb2p-depleted cells were inviable and arrested with hyper-elongated projections containing two nuclei, suggesting that Clb2p is not required for entry into mitosis. Unlike Clb2p-depleted cells, Clb4p-depleted cells were viable and formed constitutive pseudohyphae. Clb proteins lacking destruction box domains blocked cell cycle progression resulting in the formation of long projections, indicating that both Clb2p and Clb4p must be degraded before mitotic exit. In addition, overexpression of either B-type cyclin reduced the extent of filamentous growth. Taken together, these data indicate that Clb2p and Clb4p regulate C. albicans morphogenesis by negatively regulating polarized growth.

{dagger}Present address: MD Biosciences, St. Paul, MN 55108.

Address correspondence to: Judith Berman (judith{at}cbs.umn.edu)




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