Chemical screening identifies ROCK1 as a regulator of migrasome formation

Lu, Puzhong; Li, Rui; Lü, Di; Xu, Yue; Yang, Xueyi; Jiang, Zheng; Yang, Chun; Yu, Li; Lei, Xiaoguang; Chen, Yang

doi:10.1038/s41421-020-0179-6

Cited by 30 publications

(32 citation statements)

References 8 publications

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“…In contrast, the number of migrasomes was increased when accelerating cell migration by different strategies (see detail in below) [ 1 , 4 ]. Recently, Lu et al have identified 507 compounds which had significant inhibitory effect on migrasome generation, and 463 out of these 507 hits showed no or less retraction fibers indicating defect of cell migration; this further confirmed that generating migrasome is dependent on migration [ 36 ]. Based on migration-dependent biogenesis of PLSs, these PLSs were named as “migrasomes” [ 1 ].…”

Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 87%

“…Moreover, TSPAN4 was on the upper side, while the endogenous integrin α 5 and β 1 were enriched on the bottom of migrasomes, and Yu has confirmed that the integrin-enriched regions on migrasomes are not focal adhesions (FAs) [ 4 ]. The number of PLSs was increased when accelerating cell migration by knocking down SHARPIN (an endogenous inhibitor of β 1-integrin activation), and fibronectin increased migrasomes number per cell in a dose-dependent manner [ 1 , 36 , 39 ]. GLPG0187, the inhibitor of integrin α 5 β 1, inhibited the biogenesis of migrasomes in a concentration-dependent manner without cytotoxicity [ 36 ].…”

Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 99%

“…The number of PLSs was increased when accelerating cell migration by knocking down SHARPIN (an endogenous inhibitor of β 1-integrin activation), and fibronectin increased migrasomes number per cell in a dose-dependent manner [ 1 , 36 , 39 ]. GLPG0187, the inhibitor of integrin α 5 β 1, inhibited the biogenesis of migrasomes in a concentration-dependent manner without cytotoxicity [ 36 ]. The integrin α 5 mRNA levels are much higher than other examined integrins ( α 1, α 2, α 3, and α 6) in TSPAN4-GFP-expressing NRK (NRK-TSPAN4-GFP) cells [ 4 ].…”

Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 99%

“…Recently, using chemical screening and RNAi, Yu' team identifies ROCK1 (a positive regulator of microfilament bundle and focal adhesion assembly [ 40 ]), rather than ROCK2, as a regulator of migrasome formation [ 36 ]. ROCK1 contributes to the formation of migrasomes via its role in adhesion to fibronectin to generate a traction force [ 36 ]. The role of adhesion on migrasome formation has also been confirmed in vivo .…”

Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 99%

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Migrasomes: From Biogenesis, Release, Uptake, Rupture to Homeostasis and Diseases

Zhang

Guo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Migrasomes are migration-dependent membrane-bound vesicular structures that contain cellular contents and small vesicles. Migrasomes grow on the tips or intersections of the retraction fibers after cells migrate away. The process of releasing migrasomes into the extracellular space is named as “migracytosis”. After releasing, they can be taken up by the surrounding cells, or rupture and further release their contents into the extracellular environment. Physiologically, migrasomes provide regional cues for organ morphogenesis during zebrafish gastrulation and discard the damaged mitochondria in response to mild mitochondrial stresses. Pathologically, migrasomes are released from podocyte during early podocyte stress and/or damage, from platelets after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from microglia/macrophages of the ischemic brain, and from tumor necrosis factor α (TNFα)-activated endothelial cells (ECs); thus, this newly discovered extracellular vesicle is involved in all these pathological processes. Moreover, migrasomes can modulate the proliferation of cancer cell via lateral transferring mRNA and protein. In this review, we will summarize the biogenesis, release, uptake, and rupture of migrasomes and discuss its biological roles in development, redox signalling, innate immunity and COVID-19, cardio-cerebrovascular diseases, renal diseases, and cancer biology, all of these highlight the importance of migrasomes in modulating body homeostasis and diseases.

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Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 87%

Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 99%

Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 99%

Section: The Current Understanding Of Migrasome Biogenesismentioning

confidence: 99%

See 2 more Smart Citations

Migrasomes: From Biogenesis, Release, Uptake, Rupture to Homeostasis and Diseases

Zhang

Guo

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The signaling cascade mediated by VEGFA can regulate the proliferation, migration, survival of vascular endothelial cells, and control angiogenesis [ 7 , 8 ]. ROCK1 signaling modulates cell adhesion and cytoskeletal stretching upon cell migration, which has significant implications for cancer metastasis [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

miR-199a-5p Plays a Pivotal Role on Wound Healing via Suppressing VEGFA and ROCK1 in Diabetic Ulcer Foot

Wang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Diabetes mellitus (DM) is a growing health problem. As a common complication of DM, diabetic foot ulcer (DFU) results in delayed wound healing and is a leading cause of nontraumatic amputation. miR-199a-5p, a short noncoding RNA, had abnormal expression in DFU wound tissues. The expression of miR-199a-5p was significantly increased in DFU wound tissues, skin tissues of diabetic rats, and high glucose-induced cells. Vascular endothelial growth factor A (VEGFA) and Rho-associated kinase 1 (ROCK1) are directly targets of miR-199a-5p. Inhibiting the expression of miR-199a-5p alleviated the inhibition of VEGFA and ROCK1, thereby rescued impaired proliferation and migration of HG-induced cells, and restored the normal function of the cells to some extent. In diabetic rats, inhibition of miR-199a-5p significantly increased the expression of VEGFA and ROCK1, significantly promoted wound healing, and rescued impaired wound healing. miR-199a-5p and its targets showed therapeutic effect on diabetic wounds.

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The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis

Li,

Zhao,

Wang

et al. 2024

Adv Healthcare Materials

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As a newly discovered substrate anchored extracellular vesicles, migrasomes (Migs) may bring a new opportunity for manipulating target cells bioactivities. In this study, the M2 macrophages derived Migs were obtained by titania nanotubes surface (NTs). Due to the benefits of nanostructured, the NTs surface was not only able to induce RAW264.7 for M2 polarization, but also generated more Migs formation, which could be internalized by following seeded mesenchymal stem cells (MSCs). Then the NTs surface induced Migs were collected by density‐gradient centrifugation for MSCs treatment. As indicated by immunofluorescence staining, alkaline phosphatase activity and alizarin red staining, the osteogenic differentiation capacity of MSCs was significantly enhanced by Migs treatment, in line with the dosage. By RNA‐sequence analysis, the enhancement of osteogenic differentiation was correlated with PI3K‐AKT pathway activation that might be originated from the M2 polarization state of donor cells. Finally, the Migs were coated onto Ti surface for therapeutic application. Both the in vitro and in vivo analysis revealed that the Migs coated Ti implant showed significant enhancement of osteogenesis. In conclusion, this study suggests that the nanosurface may be a favorable platform for Migs production, which may bring a new concept for tissue regeneration.This article is protected by copyright. All rights reserved

show abstract

Chemical screening identifies ROCK1 as a regulator of migrasome formation

Cited by 30 publications

References 8 publications

Migrasomes: From Biogenesis, Release, Uptake, Rupture to Homeostasis and Diseases

Migrasomes: From Biogenesis, Release, Uptake, Rupture to Homeostasis and Diseases

miR-199a-5p Plays a Pivotal Role on Wound Healing via Suppressing VEGFA and ROCK1 in Diabetic Ulcer Foot

The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis

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