Candida Bem3 Regulates the Secretory Pathway During Polarized Growth

Cell polarity is the asymmetric distribution of cellular components. This feature is essential for cell migration, immune cell function and cell fate determination. The budding yeast, Saccharomyces cerevisiae, is an excellent model system for studying cell polarity. Our study focuses on the regulatory mechanisms of the Bud Emergence protein 3 (Bem3), a Rho GTPase activating protein (RhoGAP) of the master cell polarity regulator, Cdc42. Recently, our lab found that Bem3 is a cargo of the secretory machinery and that it actively plays a role in targeting secretory vesicles to sites of bud growth. We observed that overexpression of Bem3 in yeast causes accumulation of vesicles in internal compartments and that results in the sequestration of the secretory marker Sec4. Interestingly, it is known that secretion plays an essential role in the development of the invasive form (or hypha) of the pathogenic fungi, Candida albicans. Therefore, we hypothesized that Candida’s homolog of Bem3 (CaBem3) may also be involved in the regulation of the secretory pathway, and therefore, in hyphal development. In order to test this hypothesis we overexpressed CaBem3 in budding yeast and monitored Sec4 localization. In addition, we established the specific domains of CaBem3 that induce Sec4 mislocalization. Our results suggest that CaBem3 displays functional conservation with its budding yeast homolog and that it needs to localize to the endosomal compartment to affect the secretory pathway. We speculate that these studies will lead to a better understanding of the pathogenicity mechanisms operating in infectious fungi species like Candida albicans.