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

Abstract

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 in <i>Caenorhabditis elegans</i> embryos. Loss of <i>slc-36.1</i> leads to formation of phagolysosomal vacuoles arising from cell corpse-containing phagosomes. In the absence of <i>slc-36.1</i>, phagosome maturation is not affected, but the retrieval of lysosomal components is inhibited. Moreover, loss of PPK-3, the <i>C. elegans</i> 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 of <i>slc-36.1</i> and <i>ppk-3</i> 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.