Activation of Rac1 by the guanine nucleotide exchange factor Dck1 is required for invasive filamentous growth in the pathogen Candida albicans.
Rho G proteins and their regulators are critical for cytoskeleton organization and cell morphology in all eukaryotes. In the opportunistic pathogen Candida albicans, the Rho G proteins Cdc42 and Rac1 are required for the switch from budding to filamentous growth in response to different stimuli. We show that Dck1, a protein with homology to the Ced-5, Dock180, myoblast city family of guanine nucleotide exchange factors, is necessary for filamentous growth in solid media, similar to Rac1. Our results indicate that Dck1 and Rac1 do not function in the same pathway as the transcription factor Czf1, which is also required for embedded filamentous growth. The conserved catalytic region of Dck1 is required for such filamentous growth, and in vitro this region directly binds a Rac1 mutant, which mimics the nucleotide-free state. In vivo overexpression of a constitutively active Rac1 mutant, but not wild-type Rac1, in a dck1 deletion mutant restores filamentous growth. These results indicate that the Dock180 guanine nucleotide exchange factor homologue, Dck1 activates Rac1 during invasive filamentous growth. We conclude that specific exchange factors, together with the G proteins they activate, are required for morphological changes in response to different stimuli.
Hope
Hannah
H
Institute of Developmental Biology and Cancer, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6543, Université de Nice, Faculté des Sciences-Parc Valrose, 06108 Nice Cedex 2, France.
Bogliolo
Stéphanie
S
Arkowitz
Robert A
RA
Bassilana
Martine
M
D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000378:metabolism*; D020134:Catalytic Domain; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D020830:rac1 GTP-Binding Protein