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

Takeshi Nakatani, Kohei Tsujimoto, JeongHoon Park, Tatsunori Jo, Tetsuya Kimura, Yoshitomo Hayama, Hachiro Konaka, Takayoshi Morita, Yasuhiro Kato, Masayuki Nishide, Shyohei Koyama, Shigeyuki Nada, Masato Okada, Hyota Takamatsu () and Atsushi Kumanogoh ()
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Takeshi Nakatani: Osaka University
Kohei Tsujimoto: Osaka University
JeongHoon Park: Osaka University
Tatsunori Jo: Osaka University
Tetsuya Kimura: Osaka University
Yoshitomo Hayama: Osaka University
Hachiro Konaka: Osaka University
Takayoshi Morita: Osaka University
Yasuhiro Kato: Osaka University
Masayuki Nishide: Osaka University
Shyohei Koyama: Osaka University
Shigeyuki Nada: Osaka University
Masato Okada: Osaka University
Hyota Takamatsu: Osaka University
Atsushi Kumanogoh: Osaka University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23654-3

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DOI: 10.1038/s41467-021-23654-3

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