The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation

作者：Qiwen Gan, Xin Wang, Qian Zhang, Qiuyuan Yin, Youli Jian, Yubing Liu, Nan Xuan, Jinglin Li, Junxiang Zhou, Kai Liu, Yudong Jing, Xiaochen Wang, Chonglin Yang · 发表于：The Journal of Cell Biology · 年份：2019 · DOI：10.1083/jcb.201901074 · 被引用次数：38 · 研究领域：Autophagy in Disease and Therapy、Calcium signaling and nucleotide metabolism、Pancreatic function and diabetes

Phagocytic removal of apoptotic cells involves formation, maturation, and digestion of cell corpse–containing phagosomes. The retrieval of lysosomal components following phagolysosomal digestion of cell corpses remains poorly understood. Here we reveal that the amino acid transporter SLC-36.1 is essential for lysosome reformation during cell corpse clearance inCaenorhabditis elegans embryos. Loss ofslc-36.1 leads to formation of phagolysosomal vacuoles arising from cell corpse–containing phagosomes. In the absence ofslc-36.1, phagosome maturation is not affected, but the retrieval of lysosomal components is inhibited. Moreover, loss of PPK-3, theC. elegans homologue of the PtdIns3P 5-kinase PIKfyve, similarly causes accumulation of phagolysosomal vacuoles that are defective in phagocytic lysosome reformation. SLC-36.1 and PPK-3 function in the same genetic pathway, and they directly interact with one another. In addition, loss ofslc-36.1 and ppk-3 causes strong defects in autophagic lysosome reformation in adult animals. Our findings thus suggest that the PPK-3–SLC-36.1 axis plays a central role in both phagocytic and autophagic lysosome formation.