Autophagy, a cellular stress response to starvation and bacterial infection, is executed by double-membrane-bound organelles called autophagosomes. Autophagosomes transfer cytosolic material to acidified lysosomes for degradation following soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE)-dependent fusion processes. Many of the autophagy-related disorders stem from defective end-step proteolysis inside lysosomes. The role of epithelial cystic fibrosis (CF) transmembrane conductance regulator (CFTR) chloride channel has been argued to be critical for efficient lysosomal clearance; however, its context to autophagic clearance and the underlying mechanism is poorly defined. Here, we report that syntaxin17 (Stx17), an autophagic SNARE protein interacts with CFTR under nutritional stress and bacterial infection and incorporates it into mature autophagosomes to mediate an efficient lysosomal clearance. Lack of CFTR function and Stx17 and loss of CFTR-Stx17 interaction impairs bacterial clearance. We discover a specialized role of the Stx17-CFTR protein complex that is critical to prevent defective autophagy as has been the reported scenario in CF airway epithelial cells, infectious diseases, and lysosomal clearance disorders.

中文翻译：

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SNARE 蛋白 Syntaxin 17 捕获 CFTR 以增强压力下的自噬体清除

自噬是对饥饿和细菌感染的细胞应激反应，由称为自噬体的双膜结合细胞器执行。在可溶性 N-乙基马来酰亚胺敏感因子附着受体 (SNARE) 依赖性融合过程之后，自噬体将胞质物质转移到酸化的溶酶体中进行降解。许多与自噬相关的疾病源于溶酶体内有缺陷的末端蛋白水解。上皮囊性纤维化 (CF) 跨膜电导调节器 (CFTR) 氯离子通道的作用被认为对有效的溶酶体清除至关重要。然而，它与自噬清除的背景和潜在机制尚不清楚。在这里，我们报告了 syntaxin17 (Stx17)，一种自噬 SNARE 蛋白在营养压力和细菌感染下与 CFTR 相互作用，并将其整合到成熟的自噬体中以介导有效的溶酶体清除。缺乏 CFTR 功能和 Stx17 以及 CFTR-Stx17 相互作用的丧失会损害细菌清除。我们发现 Stx17-CFTR 蛋白复合物的特殊作用对于防止缺陷自噬至关重要，正如在 CF 气道上皮细胞、传染病和溶酶体清除障碍中报道的情况一样。