Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans.
Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans.
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DOI：
10.1099/00221287-148-1-191
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发表时间：
2002
期刊：
影响因子：
1.5
通讯作者：
Michael S. Waugh;Michael S. Waugh;Connie B Nichols;Connie B Nichols;Cameron M DeCesare;G. Cox;J. Heitman;J. Alspaugh
中科院分区：
文献类型：
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作者：
Michael S. Waugh;Michael S. Waugh;Connie B Nichols;Connie B Nichols;Cameron M DeCesare;G. Cox;J. Heitman;J. Alspaugh
Ras1信号转导通路控制病原菌新型隐球菌在高温下生长和交配的能力。在该生物体中鉴定出第二个RAS基因。与RAS1相比，RAS2的表达水平非常低，并且RAS2突变不会引起营养生长速率、分化或毒力因子表达的改变。在小鼠吸入性隐球菌病模型中，ras2突变株与野生型株具有相同的毒力。尽管ras1 - ras2双突变菌株是可行的，但与任何单一突变菌株相比，两种RAS基因的突变都会导致在所有温度下的生长速度下降。过表达RAS2基因完全抑制了ras1突变体的交配缺陷，部分抑制了其高温生长缺陷。在限制性温度下长时间孵育后，ras1突变体表现出肌动蛋白极性缺陷，这种缺陷也被RAS2过表达部分抑制。这些研究表明，新生隐杆线虫的Ras1和Ras2蛋白具有重叠的功能，但也具有不同的信号作用。我们的研究结果还提示了Ras1在37℃下控制病原菌生长的机制，支持Ras同源物在微生物细胞分化、形态发生和毒力中的保守作用。
The Ras1 signal transduction pathway controls the ability of the pathogenic fungus Cryptococcus neoformans to grow at high temperatures and to mate. A second RAS gene was identified in this organism. RAS2 is expressed at a very low level compared to RAS1, and a ras2 mutation caused no alterations in vegetative growth rate, differentiation or virulence factor expression. The ras2 mutant strain was equally virulent to the wild-type strain in the murine inhalational model of cryptococcosis. Although a ras1 ras2 double mutant strain is viable, mutation of both RAS genes results in a decreased growth rate at all temperatures compared to strains with either single mutation. Overexpression of the RAS2 gene completely suppressed the ras1 mutant mating defect and partially suppressed its high temperature growth defect. After prolonged incubation at a restrictive temperature, the ras1 mutant demonstrated actin polarity defects that were also partially suppressed by RAS2 overexpression. These studies indicate that the C. neoformans Ras1 and Ras2 proteins share overlapping functions, but also play distinct signalling roles. Our findings also suggest a mechanism by which Ras1 controls growth of this pathogenic fungus at 37 degrees C, supporting a conserved role for Ras homologues in microbial cellular differentiation, morphogenesis and virulence.