Rademacher Felicitas, Kehren Verena, Stoldt Volker R, Ernst Joachim F
lnstitut fur Mikrobiologie and Biologisch-Medizi nisches Forsc hu ngszentrum, Heinrich-Heine-Universitat, Universitatsstr. V26.12, D-40225 Dilsseldorf, Germany.
Microbiology (Reading). 1998 Nov;144 ( Pt 11):2951-2960. doi: 10.1099/00221287-144-11-2951.
Saccharomyces cerevisiae and the pathogen Candida albicans can be induced to undergo morphogenesis from a yeast to a filamentous form. A C. albicans gene (CaCCT8) was identified encoding a subunit of the Cct chaperonin complex, whose expression prevents filament formation in both fungi without interfering with growth of the yeast form. In S. cerevisiae, pseudohyphal growth induced by Ras2Val19, by overproduction of Phd1p or by expression of the C. albicans EFG1 gene, was blocked by CaCct8p and its N-terminally deleted derivative CaCct8-delta1p; in contrast, pseudohyphal induction by other components (Cph1p, Cdc42p) could not be suppressed, indicating that morphogenesis per se is not inhibited. CaCCT8 expression also interfered with other Ras2pVal19 phenotypes, including heat sensitivity, lack of glycogen accumulation and lack of sporulation. In C. albicans, overproduction of CaCct8p effectively blocked hyphal morphogenesis induced by starvation conditions and by serum. The results suggest that the activity of a component in the Ras2p signal transduction pathway is suppressed by excess chaperonin subunits. This component may be a novel folding target for the Cct complex. In agreement with this hypothesis, disruption of one of the two CaCCT8 alleles in C. albicans led to defective hyphal morphogenesis.
酿酒酵母和病原体白色念珠菌可被诱导从酵母形态转变为丝状形态。鉴定出一个白色念珠菌基因(CaCCT8),其编码Cct伴侣蛋白复合体的一个亚基,该基因的表达可阻止两种真菌形成丝状,且不影响酵母形态的生长。在酿酒酵母中,由Ras2Val19、Phd1p过量表达或白色念珠菌EFG1基因表达诱导的假菌丝生长,被CaCct8p及其N端缺失衍生物CaCct8 - delta1p所阻断;相反,其他成分(Cph1p、Cdc42p)诱导的假菌丝生长则无法被抑制,这表明形态发生本身并未受到抑制。CaCCT8的表达还干扰了其他Ras2pVal19表型,包括热敏感性、糖原积累缺乏和孢子形成缺乏。在白色念珠菌中,CaCct8p的过量表达有效阻断了饥饿条件和血清诱导的菌丝形态发生。结果表明,Ras2p信号转导途径中一个成分的活性被过量的伴侣蛋白亚基所抑制。该成分可能是Cct复合体的一个新的折叠靶点。与这一假设一致,白色念珠菌中两个CaCCT8等位基因之一的破坏导致了有缺陷的菌丝形态发生。