A conserved VPS34-PIKfyve-TRPML1-Myosin II axis regulates the speed of amoeboid cell migration

ABSTRACT: Amoeboid cell migration is key to efficient T cell immunity. Spatial polarization of organelles within cells, including endo-lysosomes, is a prerequisite of migration. However, how ultrastructural polarization is linked to the signaling requirements governing T cell migration remains unknown. Here we show that signaling molecules generated by endo-lysosome-localized kinases regulate velocity of amoeboid migration. Specifically, imaging of T cells identifies accumulation of endo-lysosomes decorated with the lipid kinases VPS34-PIKfyve at the uropod of polarized cells. Activity of VPS34 and PIKfyve regulates speed, but not directedness, of migrating T cells. Mechanistically, PI(3,5)P2 generated by the sequential action of VPS34 and PIKfyve, mediates Ca2+ efflux from lysosomes via the mucolip

SUBMITTER: Philippe Dehio 

PROVIDER: S-SCDT-10_1038-S44319-026-00861-X | biostudies-other |

REPOSITORIES: biostudies-other