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

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作者
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
Atsushi Kumanogoh
机构
[1] Osaka University,Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine
[2] Osaka University,Department of Immunopathology, WPI, Immunology Frontier Research Center (iFReC)
[3] Osaka University,Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives
[4] Osaka University,The Japan Science and Technology – Core Research for Evolutional Science and Technology (JST–CREST)
[5] Osaka Police Hospital,Department of Internal Medicine
[6] Osaka University,Department of Oncogene Research, Research Institute for Microbial Diseases
[7] Kinki Central Hospital,Department of Respiratory Medicine
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Nature Communications | / 12卷
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摘要
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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