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Publication : The lysosomal Ragulator complex plays an essential role in leukocyte trafficking by activating myosin II.

First Author  Nakatani T Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  3333
PubMed ID  34099704 Mgi Jnum  J:343903
Mgi Id  MGI:6725381 Doi  10.1038/s41467-021-23654-3
Citation  Nakatani T, et al. (2021) The lysosomal Ragulator complex plays an essential role in leukocyte trafficking by activating myosin II. Nat Commun 12(1):3333
abstractText  Lysosomes are involved in nutrient sensing via the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 is tethered to lysosomes by the Ragulator complex, a heteropentamer in which Lamtor1 wraps around Lamtor2-5. Although the Ragulator complex is required for cell migration, the mechanisms by which it participates in cell motility remain unknown. Here, we show that lysosomes move to the uropod in motile cells, providing the platform where Lamtor1 interacts with the myosin phosphatase Rho-interacting protein (MPRIP) independently of mTORC1 and interferes with the interaction between MPRIP and MYPT1, a subunit of myosin light chain phosphatase (MLCP), thereby increasing myosin II-mediated actomyosin contraction. Additionally, formation of the complete Ragulator complex is required for leukocyte migration and pathophysiological immune responses. Together, our findings demonstrate that the lysosomal Ragulator complex plays an essential role in leukocyte migration by activating myosin II through interacting with MPRIP.
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