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bioRxiv · 10.1101/2025.07.16.665121

VapA/Scs2 sustains polarized growth in Aspergillus nidulans by maintaining AP-2-mediated apical endocytosis

Georgiou, X.·Politi, S.·Amillis, S.·Diallinas, G.
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Abstract

Growth of filamentous fungi is highly polarized requiring the coordinated apical delivery of cell wall components and plasma membrane (PM) material, primarily lipids and proteins, to hyphal tips via conventional vesicular secretion. Fungal growth also requires the tight coordination of exocytosis (secretion) with endocytosis and recycling of proteins and lipids, which occurs in a defined region behind the growing tip known as the endocytic collar. Here, we genetically characterized proteins tentatively implicated in the formation of endoplasmic reticulum-plasma membrane (ER-PM) contact sites, including Scs2/VAP, tricalbins and Ist2 homologues, in Aspergillus nidulans. We showed that among these proteins, only the single Scs2/VapA homologue is essential for normal fungal growth, and this requirement is due to the critical role of VapA in maintaining the polarized localization of apical cargoes, such as the lipid flippases DnfA and DnfB or the SNARE protein SynA. In {Delta}vapA mutants, these cargoes lose their polarized localization, a phenotype that correlates with the mislocalization of the AP-2 cargo adaptor complex, which is essential for the endocytosis and recycling of apical membrane components. Further analysis provides evidence linking the defect in apical cargo endocytosis observed in {Delta}vapA mutants to altered membrane lipid partitioning, suggesting that VapA contributes to lipid domain organization critical for cargo recycling. Strikingly, deletion of VapA does not impair the localization or endocytosis of non-polarized (subapical) plasma membrane transporters, indicating that the trafficking and biogenesis of polarized (apical) versus non-polarized (subapical) cargoes are differentially dependent on membrane lipid composition and domain-specific organization.

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Georgiou, X., Politi, S., Amillis, S., Diallinas, G.. 2025-07-16. VapA/Scs2 sustains polarized growth in Aspergillus nidulans by maintaining AP-2-mediated apical endocytosis. https://doi.org/10.1101/2025.07.16.665121

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