The late endosome/lysosome-anchored p18-mTORC1 pathway controls terminal maturation of lysosomes

The late endosome/lysosome membrane adaptor p18 (or LAMTOR1) serves as an anchor for the mammalian target of rapamycin complex 1 (mTORC1) and is required for its activation on lysosomes. The loss of p18 causes severe defects in cell growth as well as endosome dynamics, including membrane protein transport and lysosome biogenesis. However, the mechanisms underlying these effects on lysosome biogenesis remain unknown. Here, we show that the p18-mTORC1 pathway is crucial for terminal maturation of lysosomes. The loss of p18 causes aberrant intracellular distribution and abnormal sizes of late endosomes/lysosomes and an accumulation of late endosome specific components, including Rab7, RagC, and LAMP1; this suggests that intact late endosomes accumulate in the absence of p18. These defects are phenocopied by inhibiting mTORC1 activity with rapamycin. Loss of p18 also suppresses the integration of late endosomes and lysosomes, resulting in the defective degradation of tracer proteins. These results suggest that the p18-mTORC1 pathway plays crucial roles in the late stages of lysosomal maturation, potentially in late endosome–lysosome fusion, which is required for processing of various macromolecules.

► p18 is a membrane adaptor that anchors mTORC1 to late endosomes/lysosomes.
► We examine the role of the p18-mTORC1 pathway in lysosome biogenesis.
► The loss of p18 causes accumulation of intact late endosomes by arresting lysosome maturation.
► Inhibition of mTORC1 activity with rapamycin phenocopies the defects of p18 loss.
► The p18-mTORC1 pathway plays crucial roles in the terminal maturation of lysosomes.