Title: | "The conserved dual phosphorylation sites of the Candida albicans Hog1 protein are crucial for white-opaque switching, mating, and pheromone-stimulated cell adhesion" |
Author(s): | Chang WH; Liang SH; Deng FS; Lin CH; |
Address: | "Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan. Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan chinghsuanlin@ntu.edu.tw" |
ISSN/ISBN: | 1460-2709 (Electronic) 1369-3786 (Linking) |
Abstract: | "Candida albicans is an opportunistic human pathogen capable of causing life-threatening infections in immunocompromised patients. C. albicans has a unique morphological transition between white and opaque phases. These two cells differ in virulence, mating capability, biofilm formation, and host-cell interaction. Previous studies revealed that deletion of the SSK2, PBS2, or HOG1 gene resulted in 100% opaque cell formation and suppressed the mating response. Thr-174 and Tyr-176 of the Hog1 protein are important phosphoacceptors and can be activated in response to stimuli. In this study, we first demonstrated the importance of two conserved phosphorylation sites in white-opaque switching, mating, and pheromone-stimulated cell adhesion. Six Hog1 point-mutated strains were generated, including nonphosphorylated strains (Hog1(T174A), Hog1(Y176F), and Hog1(T174A,Y176F)) and negatively charged phosphorylated strains (Hog1(T174D), Hog1(Y176D), and Hog1(T174D,Y176D)). Point mutation on Thr-174, Tyr-176 or in combination with the Hog1 protein in C. albicans MTL homozygous strains stimulated opaque cell formation at a frequency of 100%. Furthermore, mating projections of point-mutated strains were significantly shorter and their mating efficiencies and pheromone-stimulated cell adhesive numbers were lower than those of the wild-type. By investigating the effects of Hog1 phosphorylation in ssk1Delta and sln1Delta, we also demonstrate that the phosphorylation intensity of Hog1p is directly involved in the white-opaque switching. Taken together, the results of our study demonstrate that dual phosphorylation sites of C. albicans are crucial for white-opaque transition, sexual mating, and pheromone-induced cell adhesion" |
Keywords: | "Candida albicans/drug effects/genetics/*physiology *Cell Adhesion DNA Mutational Analysis Fungal Proteins/genetics/*metabolism Gene Expression Regulation, Fungal Humans Mutation, Missense *Phenotype Pheromones/metabolism Phosphorylation Point Mutation *Pr;" |
Notes: | "MedlineChang, Wen-Han Liang, Shen-Huan Deng, Fu-Sheng Lin, Ching-Hsuan eng England 2016/04/28 Med Mycol. 2016 Aug 1; 54(6):628-40. doi: 10.1093/mmy/myw015. Epub 2016 Apr 26" |