The lysosomal Ragulator complex plays an essential role in leukocyte trafficking by activating myosin II.
Actomyosin
/ drug effects
Adaptor Proteins, Signal Transducing
/ metabolism
Animals
Cell Line
Dendritic Cells
Female
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Leukocytes
/ metabolism
Lysosomes
/ metabolism
Male
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Mice
Mice, Inbred C57BL
Myosin Type II
/ metabolism
Myosin-Light-Chain Phosphatase
Neutrophils
Signal Transduction
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 06 2021
07 06 2021
Historique:
received:
30
01
2020
accepted:
27
04
2021
entrez:
8
6
2021
pubmed:
9
6
2021
medline:
23
6
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34099704
doi: 10.1038/s41467-021-23654-3
pii: 10.1038/s41467-021-23654-3
pmc: PMC8184920
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Intracellular Signaling Peptides and Proteins
0
LAMTOR1 protein, human
0
MPRIP protein, human
0
Actomyosin
9013-26-7
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Myosin-Light-Chain Phosphatase
EC 3.1.3.53
PPP1R12A protein, human
EC 3.1.3.53
Myosin Type II
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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