Evidence map›Paper›PMID 40494613›Full record

ArticleLife science alliance2025

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

Tatsunori Jo, Kohei Tsujimoto, Takeshi Nakatani, Daiki Nagira, Yutaka Muto, Takehiro Hirayama, Hachiro Konaka, Masato Okada, Hyota Takamatsu, Atsushi Kumanogoh

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Article in Life science alliance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Tatsunori JoDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.ORCID 0000-0001-5435-3723
Kohei TsujimotoDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.ORCID 0000-0001-6958-2983
Takeshi NakataniDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Daiki NagiraDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yutaka MutoDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Takehiro HirayamaDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Hachiro KonakaDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Masato OkadaDepartment of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Hyota TakamatsuDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan thyota@imed3.med.osaka-u.ac.jp.ORCID 0000-0002-0382-5142
Atsushi KumanogohDepartment of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan kumanogo@imed3.med.osaka-u.ac.jp.ORCID 0000-0003-4749-7117

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 activation, thereby suppressing cell migration. Therapeutically, ouabain ameliorated the severity of MSU-induced gouty arthritis and LPS-induced lung injury in mice by inhibiting leukocyte infiltration. Overall, lysosomes facilitate the interaction between the Ragulator complex and MPRIP by supplying calcium ions through TRPML1 channels, thereby activating myosin IIA and promoting leukocyte migration.

Indexed as

Adaptor Proteins, Signal TransducingCalciumCell MovementLysosomesAnimalsHumansLeukocytesMaleMiceMice, Inbred C57BLNonmuscle Myosin Type IIATransient Receptor Potential ChannelsAdaptor Proteins, Signal TransducingCalciumNonmuscle Myosin Type IIATransient Receptor Potential Channels

Identifiers

PMID40494613
PMCPMC12152492

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.