Fungal pathogens are platforms for discovering novel and conserved septin properties

Abstract

Septins are filament-forming GTP-binding proteins that act as scaffolds in diverse cell functions including division, polarity and membrane remodeling. In a variety of fungal pathogens, it has been observed that septins are required for virulence because cells are unable to survive or are misshapen when septins are mutated. Cell morphology is interconnected with pathogenesis and thus septin mutants displaying aberrant cell morphologies are commonly deficient in host tissue invasion. The degree to which septins orchestrate versus maintain changes in fungal cell morphology during pathogenesis remains to be determined. Aside from the importance of septins in the process of pathogenesis, animal and plant fungal pathogens display complexity in septin form, dynamics, and function not seen in Saccharomyces cerevisiae making these organisms important models for uncovering diversity in septin behavior. Additionally, host septins have recently been implicated in the process of Candida albicans invasion, motivating the need to examine host septins in fungal pathogenesis. Understanding the role of septins in the host-pathogen interaction not only illuminates pathogenesis mechanisms but importantly also expands our understanding of septin biology in general.

Figure 1

Septin localization and dynamics. (a) In S. cerevisiae, septins localize to the bud-neck plasma membrane in a gauze-like arrangement of filaments that act as molecular scaffolds for many proteins, some of which preferentially localize to one side of the bud-neck [4]. Septin higher-order structures assemble from palindromic rod subunits via a process involving filament annealing and once assembled are capable of restricting membrane associated proteins to one side of the cell [3,22]. (b) In the plant pathogen U. maydis, septins Sep1, Sep2, and Sep3 localize to the cell middle and at growing tips [30]. Notably, Sep4 also localizes at these sites but additionally forms fibers structures running throughout the cell, which partially colocalize with, but do not depend on, microtubules [30]. (c) Though all septins colocalize in C. albicans hyphae, their dynamics are separable. While Cdc3, Cdc11, Cdc12 and Shs1 assembled into higher order structures do not readily exchange with cytoplasmic septins as determined by FRAP, Cdc10 does. Interestingly, Cdc10, the only septin lacking a c-terminal coiled-coil domain, was found to recover after photobleaching only when Shs1 was not mutated [29].

Figure 2

Septins are required for proper cell morphology. (a) While wild type S. cerevisiae cells undergo an apical to isotropic growth transition early in budding, temperature sensitive septin mutants skip this Swe1 mediated checkpoint [41]. (b) U. maydis cells in which individual septin genes have been deleted remain viable yet display strong morphology defects that are not restricted to one region of the cell. These defects are alleviated upon growth in media containing sorbitol, suggesting aberrant shapes could be due to cell wall imperfections [30]. (c) In C. albians cdc3Δ, cdc12Δ, and cdc12-6 mutants grow with curved hyphae that are unable to appreciably invade host tissues. Additionally, these mutants form new germ tubes axial to the original, unlike wild type cells in which the site of polarity is random, suggesting a role for septins in establishing or maintaining cell polarity [13,44*]. (d) In U. maydis, Cdc3 is translated on endosomes traveling to growing cell tips [48**]. Are the other septins translated on the same endosomes? Could this be the basis for septin complex formation?