Figure 4.

Interplay between lysosome position and function and nutrient signals regulated by PIs. In the absence of nutrients and growth factors, lysosomes are transported retrogradely via dynein motors linked via Rab7/RILP. Growth factor deprivation also triggers PI3KC2β recruitment to lysosomes, where it generates PI(3,4)P₂ to suppress mTORC1 activity, and facilitates perinuclear clustering of lysosomes. High nutrient and growth factor conditions cause activation of the class III PI3K Vps34. Vps34-mediated synthesis of PI(3)P results in lysosomal recruitment of the kinesin 1 adaptor FYCO1, which may supply kinesin motors to the Arl8-associated adaptor SKIP/PLEKHM2. Lysosomes undergo anterograde transport resulting in their dispersion to the cell periphery and in activation of mTORC1, e.g. by growth factor-derived Akt signaling.