Human YKT6 forms priming complex with STX17 and SNAP29 to facilitate autophagosome-lysosome fusion.

Autophagy is crucial for degrading and recycling cellular components. Fusion between autophagosomes and lysosomes is pivotal, directing autophagic cargo to degradation. This process is driven by STX17-SNAP29-VAMP8 and STX7-SNAP29-YKT6 in mammalian cells. However, the interaction between STX17 and YKT6 and its significance remain to be revealed. In this study, we challenge the notion that STX17 and YKT6 function independently in autophagosome-lysosome fusion. YKT6, through its SNARE domain, forms a complex with STX17 and SNAP29 on autophagosomes, enhancing autophagy flux. VAMP8 displaces YKT6 from this complex, leading to the formation of the fusogenic complex STX17-SNAP29-VAMP8. We demonstrated that the YKT6-SNAP29-STX17 complex facilitates both lipid and content mixing driven by STX17-SNAP29-VAMP8, suggesting a priming role of YKT6 for efficient membrane fusion. Our results provide a potential regulation mechanism of autophagosome-lysosome fusion, highlighting the importance of YKT6 and its interactions with STX17 and SNAP29 in promoting autophagy flux.

The Non-Histone Protein FgNhp6 Is Involved in the Regulation of the Development, DON Biosynthesis, and Virulence of Fusarium graminearum.

Fusarium graminearum is the primary causative agent of Fusarium head blight (FHB), a devastating disease affecting cereals globally. The high-mobility group (HMG) of non-histone proteins constitutes vital architectural elements within chromatin, playing diverse roles in various biological processes in eukaryotic cells. Nonetheless, the specific functions of HMG proteins in F. graminearum have yet to be elucidated. Here, we identified 10 HMG proteins in F. graminearum and extensively characterized the biological roles of one HMGB protein, FgNhp6. We constructed the FgNhp6 deletion mutant and its complementary strains. With these strains, we confirmed the nuclear localization of FgNhp6 and discovered that the absence of FgNhp6 led to reduced radial growth accompanied by severe pigmentation defects, a significant reduction in conidial production, and a failure to produce perithecia. The ∆FgNhp6 mutant exhibited a markedly reduced pathogenicity on wheat coleoptiles and spikes, coupled with a significant increase in deoxynivalenol production. An RNA sequencing (RNA-seq) analysis indicated that FgNhp6 deletion influenced a wide array of metabolic pathways, particularly affecting several secondary metabolic pathways, such as sterol biosynthesis and aurofusarin biosynthesis. The findings of this study highlight the essential role of FgNhp6 in the regulation of the asexual and sexual reproduction, deoxynivalenol (DON) production, and pathogenicity of F. graminearum.