The Candida albicans ELMO homologue functions together with Rac1 and Dck1, upstream of the MAP Kinase Cek1, in invasive filamentous growth.
Regulation of Rho G-proteins is critical for cytoskeletal organization and cell morphology in all eukaryotes. In the human opportunistic pathogen Candida albicans, Rac1 and its activator Dck1, a member of the CED5, Dock180, myoblast city family of guanine nucleotide exchange factors, are required for the budding to filamentous transition during invasive growth. We show that Lmo1, a protein with similarity to human ELMO1, is necessary for invasive filamentous growth, similar to Rac1 and Dck1. Furthermore, Rac1, Dck1 and Lmo1 are required for cell wall integrity, as the deletion mutants are sensitive to cell wall perturbing agents, but not to oxidative or osmotic stresses. The region of Lmo1 encompassing the ELMO and PH-like domains is sufficient for its function. Both Rac1 and Dck1 can bind Lmo1. Overexpression of a number of protein kinases in the rac1, dck1 and lmo1 deletion mutants indicates that Rac1, Dck1 and Lmo1 function upstream of the mitogen-activated protein kinases Cek1 and Mkc1, linking invasive filamentous growth to cell wall integrity. We conclude that the requirement of ELMO/CED12 family members for Rac1 function is conserved from fungi to humans.
Hope
Hannah
H
Institute of Developmental Biology and Cancer, CNRS UMR 6543, Université de Nice - Sophia Antipolis, Faculté des Sciences-Parc Valrose, 06108 Nice Cedex 2, France.
Schmauch
Christian
C
Arkowitz
Robert A
RA
Bassilana
Martine
M
D002176:Candida albicans / Q000166:cytology* / Q000254:growth & development*; D002473:Cell Wall / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008853:Microscopy; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C077339:CEK1 protein, Candida albicans; D048052:Mitogen-Activated Protein Kinase 3; D020830:rac1 GTP-Binding Protein