Autophagosome–lysosome fusion mediated by SNARE complexes is an essential step in autophagy. Two SNAP29-containing SNARE complexes have been extensively studied in starvation-induced bulk autophagy, while the relevant SNARE complexes in other types of autophagy occurring under non-starvation conditions have been overlooked. Here, we found that autophagosome–lysosome fusion in selective autophagy under non-starvation conditions does not require SNAP29-containing SNARE complexes, but requires the STX17-SNAP47-VAMP7/VAMP8 SNARE complex. Further, the STX17-SNAP47-VAMP7/VAMP8 SNARE complex also functions in starvation-induced autophagy. SNAP47 is recruited to autophagosomes following concurrent detection of ATG8s and PI(4,5)P 2 via its Pleckstrin homology domain. By contrast, SNAP29-containing SNAREs are excluded from selective autophagy due to inactivation by O-GlcNAcylation under non-starvation conditions. These findings depict a previously unknown, default SNARE complex responsible for autophagosome–lysosome fusion in both selective and bulk autophagy, which could guide research and therapeutic development in autophagy-related diseases.
You Wu,Jiaojiao Li,Wenjiao Ding,Zheng Ruan,Li Zhang
The intestinal barrier is essential for maintaining human intestinal health. The growing number of studies has shown that both puerarin and tryptophan and its metabolites have a beneficial effect on the intestinal barrier. This study aims at the combination of puerarin and tryptophan or its metabolites for improving the intestinal barrier. In our study, 40 female Sprague–Dawley rats were randomly divided into five groups (n = 8) for a 4-week experiment and dextran sodium sulfate was used to induce an intestinal barrier injury in rats. Our results showed that puerarin combined with tryptophan or its metabolites (indole-3-propionic acid, IPA) improved the intestinal barrier by enhancing the mucus layer barrier, which was mainly achieved by increasing the number of goblet cells and promoting the secretion of MUC2. Both TRPM5 and VAMP8 promoted MUC2 secretion in goblet cells through exocytosis, but their mechanisms of action are different. In our study, we found that puerarin and tryptophan showed different effects on TRPM5 and VAMP8, respectively. Puerarin enhances the expression of TRPM5, and tryptophan inhibits the expression of TRPM5; however, puerarin and tryptophan have no significant effect on the expression of VAMP8.
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