Brand Alexandra, Vacharaksa Anjalee, Bendel Catherine, Norton Jennifer, Haynes Paula, Henry-Stanley Michelle, Wells Carol, Ross Karen, Gow Neil A R, Gale Cheryl A
Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
Eukaryot Cell. 2008 Apr;7(4):712-20. doi: 10.1128/EC.00453-07. Epub 2008 Feb 15.
Directional growth is a function of polarized cells such as neurites, pollen tubes, and fungal hyphae. Correct orientation of the extending cell tip depends on signaling pathways and effectors that mediate asymmetric responses to specific environmental cues. In the hyphal form of the eukaryotic fungal pathogen Candida albicans, these responses include thigmotropism and galvanotropism (hyphal turning in response to changes in substrate topography and imposed electrical fields, respectively) and penetration into semisolid substrates. During vegetative growth in C. albicans, as in the model yeast Saccharomyces cerevisiae, the Ras-like GTPase Rsr1 mediates internal cellular cues to position new buds in a prespecified pattern on the mother cell cortex. Here, we demonstrate that Rsr1 is also important for hyphal tip orientation in response to the external environmental cues that induce thigmotropic and galvanotropic growth. In addition, Rsr1 is involved in hyphal interactions with epithelial cells in vitro and its deletion diminishes the hyphal invasion of kidney tissue during systemic infection. Thus, Rsr1, an internal polarity landmark in yeast, is also involved in polarized growth responses to asymmetric environmental signals, a paradigm that is different from that described for the homologous protein in S. cerevisiae. Rsr1 may thereby contribute to the pathogenesis of C. albicans infections by influencing hyphal tip responses triggered by interaction with host tissues.
定向生长是神经突、花粉管和真菌菌丝等极化细胞的一种功能。延伸的细胞顶端的正确定向取决于介导对特定环境线索的不对称反应的信号通路和效应器。在真核真菌病原体白色念珠菌的菌丝形态中,这些反应包括向触性和向电性(分别是菌丝响应底物地形变化和施加的电场而转向)以及穿透进入半固体底物。在白色念珠菌的营养生长过程中,如同在模式酵母酿酒酵母中一样,类Ras GTP酶Rsr1介导细胞内线索,以在母细胞皮层上以预先指定的模式定位新的芽。在这里,我们证明Rsr1对于响应诱导向触性和向电性生长的外部环境线索的菌丝顶端定向也很重要。此外,Rsr1在体外参与菌丝与上皮细胞的相互作用,其缺失会减少全身感染期间菌丝对肾脏组织的侵袭。因此,酵母中的一个内部极性标志物Rsr1也参与对不对称环境信号的极化生长反应,这一模式与酿酒酵母中同源蛋白所描述的模式不同。Rsr1可能因此通过影响与宿主组织相互作用触发的菌丝顶端反应而有助于白色念珠菌感染的发病机制。