Gale C, Gerami-Nejad M, McClellan M, Vandoninck S, Longtine M S, Berman J
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Mol Biol Cell. 2001 Nov;12(11):3538-49. doi: 10.1091/mbc.12.11.3538.
The ability to switch between yeast and hyphal morphologies is an important virulence factor for the opportunistic pathogen Candida albicans. Although the kinetics of appearance of the filamentous ring that forms at the incipient septum differ in yeast and cells forming hyphae (germ tubes) (), the molecular mechanisms that regulate this difference are not known. Int1p, a C. albicans gene product with similarity in its C terminus to Saccharomyces cerevisiae Bud4p, has a role in hyphal morphogenesis. Here we report that in S. cerevisiae, Int1p expression results in the growth of highly polarized cells with delocalized chitin and defects in cytokinesis and bud-site selection patterns, phenotypes that are also seen in S. cerevisiae septin mutant strains. Expression of high levels of Int1p in S. cerevisiae generated elaborate spiral-like structures at the periphery of the polarized cells that contained septins and Int1p. In addition, Int1p coimmunoprecipitated with the Cdc11p and Cdc12p septins, and Cdc12p is required for the establishment and maintenance of these Int1p/septin spirals. Although Swe1p kinase contributes to INT1-induced filamentous growth in S. cerevisiae, it is not required for the formation of ectopic Int1p/septin structures. In C. albicans, Int1p was important for the axial budding pattern and colocalized with Cdc3p septin in a ring at the mother-bud neck of yeast and pseudohyphal cells. Under conditions that induce hyphae, both Cdc3p and Int1p localized to a ring distal to the junction of the mother cell and germ tube. Thus, placement of the Int1p/septin ring with respect to the mother-daughter cell junction distinguishes yeast/pseudohyphal growth from hyphal growth in C. albicans.
在酵母形态和菌丝形态之间进行转换的能力是机会性病原体白色念珠菌的一个重要毒力因子。尽管在酵母和形成菌丝(芽管)的细胞中,在初始隔膜处形成的丝状环的出现动力学有所不同(),但调节这种差异的分子机制尚不清楚。Int1p是白色念珠菌的一种基因产物,其C末端与酿酒酵母的Bud4p相似,在菌丝形态发生中起作用。在此我们报告,在酿酒酵母中,Int1p的表达导致高度极化细胞的生长,这些细胞具有脱定位的几丁质,并且在胞质分裂和芽位选择模式方面存在缺陷,这些表型在酿酒酵母的隔膜蛋白突变菌株中也可见。在酿酒酵母中高水平表达Int1p会在极化细胞的周边产生精细的螺旋状结构,这些结构包含隔膜蛋白和Int1p。此外,Int1p与Cdc11p和Cdc12p隔膜蛋白共免疫沉淀,并且Cdc12p是这些Int1p/隔膜蛋白螺旋结构的建立和维持所必需的。尽管Swe1p激酶有助于酿酒酵母中INT1诱导的丝状生长,但异位Int1p/隔膜蛋白结构的形成并不需要它。在白色念珠菌中,Int1p对轴向出芽模式很重要,并且在酵母和假菌丝细胞的母-芽颈部的环中与Cdc3p隔膜蛋白共定位。在诱导菌丝的条件下,Cdc3p和Int1p都定位在母细胞和芽管连接处远端的环上。因此,Int1p/隔膜蛋白环相对于母-子细胞连接处的位置区分了白色念珠菌中酵母/假菌丝生长与菌丝生长。