Butler David K, All Ojay, Goffena Joy, Loveless Timothy, Wilson Ted, Toenjes Kurt A
Department of Biological and Physical Sciences, Montana State University-Billings, 59101, USA.
Fungal Genet Biol. 2006 Aug;43(8):573-82. doi: 10.1016/j.fgb.2006.03.004. Epub 2006 May 26.
The opportunistic fungal pathogen Candida albicans can grow as yeast, pseudohyphae or true hyphae. C. albicans can switch between these morphologies in response to various environmental stimuli and this ability to switch is thought to be an important virulence trait. In Saccharomyces cerevisiae, the Grr1 protein is the substrate recognition component of an SCF ubiquitin ligase that regulates cell cycle progression, cell polarity and nutrient signaling. In this study, we have characterized the GRR1 gene of C. albicans. Deletion of GRR1 from the C. albicans genome results in a highly filamentous, pseudohyphal morphology under conditions that normally promote the yeast form of growth. Under hypha-inducing conditions, most cells lacking GRR1 retain a pseudohyphal morphology, but some cells appear to switch to hyphal-like growth and express the hypha-specific genes HWP1 and ECE1. The C. albicans GRR1 gene also complements the elongated cell morphology phenotype of an S. cerevisiae grr1Delta mutant, indicating that C. albicans GRR1 encodes a true orthologue of S. cerevisaie Grr1. These results support the hypothesis that the Grr1 protein of C. albicans, presumably as the F-box subunit of an SCF ubiquitin ligase, has an essential role in preventing the switch from the yeast cell morphology to a pseudohyphal morphology.
机会性真菌病原体白色念珠菌可呈酵母、假菌丝或真菌丝形态生长。白色念珠菌能够根据各种环境刺激在这些形态之间转换,而这种转换能力被认为是一种重要的毒力特性。在酿酒酵母中,Grr1蛋白是SCF泛素连接酶的底物识别成分,该连接酶调节细胞周期进程、细胞极性和营养信号传导。在本研究中,我们对白色念珠菌的GRR1基因进行了表征。从白色念珠菌基因组中缺失GRR1会导致在通常促进酵母生长形式的条件下出现高度丝状的假菌丝形态。在菌丝诱导条件下,大多数缺乏GRR1的细胞保持假菌丝形态,但一些细胞似乎会转变为类似菌丝的生长并表达菌丝特异性基因HWP1和ECE1。白色念珠菌GRR1基因还能弥补酿酒酵母grr1Δ突变体的细长细胞形态表型,这表明白色念珠菌GRR1编码酿酒酵母Grr1的真正同源物。这些结果支持了这样一种假设,即白色念珠菌的Grr1蛋白,可能作为SCF泛素连接酶的F-box亚基,在防止从酵母细胞形态转变为假菌丝形态方面具有重要作用。