Septins Focus Cellular Growth for Host Infection by Pathogenic Fungi

Abstract

One of the key challenges faced by microbial pathogens is invasion of host tissue. Fungal pathogens adopt a number of distinct strategies to overcome host cell defenses, including the development of specialized infection structures, the secretion of proteins that manipulate host responses or cellular organization, and the ability to facilitate their own uptake by phagocytic mechanisms. Key to many of these adaptations is the considerable morphogenetic plasticity displayed by pathogenic species. Fungal pathogens can, for example, shift their growth habit between non-polarized spores, or yeast-like cells, and highly polarized hyphal filaments. These polarized filaments can then elaborate differentiated cells, specialized to breach host barriers. Septins play fundamental roles in the ability of diverse fungi to undergo shape changes and organize the F-actin cytoskeleton to facilitate invasive growth. As a consequence, septins are increasingly implicated in fungal pathogenesis, with many septin mutants displaying impairment in their ability to cause diseases of both plants and animals. In this mini-review, we show that a common feature of septin mutants is the emergence of extra polar outgrowths during morphological transitions, such as emergence of germ tubes from conidia or branches from hyphae. We propose that because septins detect and stabilize membrane curvature, they prevent extra polar outgrowths and thereby focus fungal invasive force, allowing substrate invasion.

Secretory Vesicle Polar Sorting, Endosome Recycling and Cytoskeleton Organization Require the AP-1 Complex in Aspergillus nidulans

“…Lack of such cell-end markers is known to result in curved or zigzagged organization of MTs and less straight hyphae, compatible with the picture we obtained in the AP-1 null mutant. Importantly, we further supported the essential role of AP-1 in MT organization and function by showing the dramatic effect of the absence of AP-1 on the subcellular organization of septins, proteins that play fundamental roles in the ability of diverse fungi to undergo shape changes and organize the cytoskeleton for polar growth (Momany and Talbot 2017;Zhang et al 2017).…”

The AP-1 complex is essential for fungal growth via its role in secretory vesicle polar sorting, endosomal recycling and cytoskeleton organization

“…Lack of such cell-end markers is known to result in curved or zigzagged organization of MTs and less straight hyphae, compatible with the picture we obtained in the AP-1 null mutant. Importantly, we further supported the essential role of AP-1 in MT organization and function by showing the dramatic effect of the absence of AP-1 on the subcellular organization of septins, proteins that play fundamental roles in the ability of diverse fungi to undergo shape changes and organize the cytoskeleton for polar growth (Zhang et al, 2017; Momany and Talbot, 2017).…”

“…Septins are less well characterized GTP-binding proteins, which form hetero-polymers associating into higher order structures, and are thought to play a central role in the spatial regulation and coordination of the actin and microtubule networks in most eukaryotes (Mostowy and Cossart, 2012; Spiliotis, 2018). In A. nidulans , five septins have been under investigation, the four core septins AspA-D, which form hetero-polymers appearing in various shapes, including spots, rings and filaments, and a fifth septin of currently unknown function, AspE, not involved in the hetero-polymer and appearing as dense cortical spots at the proximity of the plasma membrane (Hernadez Rodriguez and Momany, 2012; Hernadez Rodriguez et al, 2014; Momany and Talbot, 2017). Figure 6E shows that upon AP-1 repression, hetero-polymer forming core septins AspB, AspC and AspD appear less in the form of filamentous structures, while distinct bright cortical spots tend to accumulate at the hyphal periphery, several of which possibly mark positions of new septa, in agreement with increased numbers of septa observed in the absence of AP-1.…”

MCC/Eisosomes Regulate Cell Wall Synthesis and Stress Responses in Fungi

“…In addition to acting in septation, septins guide proper cell wall synthesis during different types of highly polarized cell growth [ 92 ]. For example, septins act in pheromone-induced morphogenesis in S. cerevisiae to promote formation of the conjugation bridge that connects mating cells [ 93 , 94 ].…”