The Ragulator complex and lysosomal calcium release are crucial for cell migration.

ABSTRACT: Immune cells migrate via actomyosin contractility mediated by myosin IIA activation, wherein the lysosomal Ragulator complex-MPRIP interaction is crucial. However, the precise mechanism underlying lysosome-mediated myosin IIA activation has not been elucidated. Here, we found that calcium efflux from the lysosomal TRPML1 channel promotes leukocyte trafficking by enhancing the interaction between the Ragulator complex and MPRIP. Disrupting the lysosome-anchoring site of Lamtor1 impaired the localization of the Ragulator complex to lysosomes, diminishing the TRPML1-mediated leukocyte migration and interaction between Lamtor1 and MPRIP. Furthermore, ouabain, a cardiac glycoside, dissociated Lamtor1 from lysosomes, inhibiting the interaction between the Ragulator complex and myosin IIA activat

SUBMITTER: Jo T 

PROVIDER: S-EPMC12152492 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature