Calmodulin Binding to Dfi1p Promotes Invasiveness of Candida albicans
Calmodulin Binding to Dfi1p Promotes Invasiveness of Candida albicans
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DOI：
10.1371/journal.pone.0076239
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发表时间：
2013-10-14
期刊：
影响因子：
3.7
通讯作者：
Kumamoto, Carol A.
中科院分区：
文献类型：
--
作者：
Davis, Talya R.;Zucchi, Paola C.;Kumamoto, Carol A.
白色念珠菌是一种二态真菌，在许多不同的环境条件下发生菌丝发育，包括与半固体基质接触的生长。当细胞嵌入或生长在琼脂表面时，白色念珠菌形成侵入琼脂的菌丝，而这种活性需要完整的膜蛋白Dfi1p。此外，Dfi1p是在琼脂上生长过程中丝裂原活化蛋白激酶Cek1p完全激活所必需的。在这项研究中，我们在Dfi1p的c端尾部发现了一个假定的钙调蛋白结合基序。Dfi1p的这一区域在体外与钙调蛋白结合，影响该区域的突变既影响体外钙调蛋白结合，也影响全长Dfi1p蛋白的侵入性丝化。此外，细胞内钙水平升高导致钙依赖性、dfi1p依赖性Cek1p激活。我们提出，Dfi1p的构象变化响应生长过程中遇到的环境条件，允许蛋白质结合钙调蛋白并启动激活Cek1p的信号级联。
Candida albicans, a dimorphic fungus, undergoes hyphal development in response to many different environmental cues, including growth in contact with a semi-solid matrix. C. albicans forms hyphae that invade agar when cells are embedded in or grown on the surface of agar, and the integral membrane protein Dfi1p is required for this activity. In addition, Dfi1p is required for full activation of mitogen activated protein kinase Cek1p during growth on agar. In this study, we identified a putative calmodulin binding motif in the C-terminal tail of Dfi1p. This region of Dfi1p bound to calmodulin in vitro, and mutations that affected this region affected both calmodulin binding in vitro and invasive filamentation when incorporated into the full length Dfi1p protein. Moreover, increasing intracellular calcium levels led to calcium-dependent, Dfi1p-dependent Cek1p activation. We propose that conformational changes in Dfi1p in response to environmental conditions encountered during growth allow the protein to bind calmodulin and initiate a signaling cascade that activates Cek1p.