Unraveling Vps1-mediated endolysosomal sorting as a potential target for effective fungal disease control

During host-pathogen interactions, fungal pathogens exploit the endolysosomal trafficking network to fine-tune their responses to host and environmental stimuli, thereby facilitating disease progression. However, the molecular mechanisms underlying the fungal-specific functions of the endolysosomal network require further investigation. Here, we systematically characterized the endolysosomal network in Fusarium graminearum using the dynamin-like GTPase FgVps1 as an entry point. Functional analysis revealed that FgVps1 is essential for the release of retromer- and sorting nexin-associated vesicles from endosomes, thereby facilitating the trafficking of v-SNARE protein FgSnc1 and promoting fungal development and pathogenicity. Building on this, we further discovered that the retromer core subunit FgVps35 interacts with sorting nexin FgSnx4 and identified the corresponding interaction interface, which involves residues FgVps35^N383 and FgSnx4^E373. In addition, the ESCRT-II component FgVps36 bridges ESCRT-I and ESCRT-III and interacts with both FgVps35 and FgSnx4, thereby preventing their mislocalization to the vacuole and maintaining endolysosomal trafficking. Notably, we demonstrated that inhibition of FgVps1 function, either by blocking its GTPase activity or by disrupting actin polymerization, effectively impaired endosomal trafficking and attenuates fungal pathogenicity. Altogether, our results provide insight into the mechanisms underlying the function of the fungal endolysosomal network and suggest a promising broad-spectrum strategy for controlling phytopathogenic fungi.