Talin-2 regulates integrin functions in exosomes

Soe, Zay Yar; Prajuabjinda, Onmanee; Myint, Phyoe Kyawe; Gaowa, Arong; Kawamoto, Eiji; Park, Eun Jeong; Shimaoka, Motomu

doi:10.1016/j.bbrc.2019.03.027

Cited by 16 publications

(14 citation statements)

References 33 publications

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“…Integrin beta 2 is a multifunctional protein that is crucial for efficient cell binding to extracellular matrix. Integrins are also localized on the surface of EVs, where they interact with, for example, FN [86] and cytoskeletal proteins, for example, talin and tubulin [80,81].…”

Section: Proteins Detected Only In Evs Shed By Apap-treated Livermentioning

confidence: 99%

Changes in the proteome of extracellular vesicles shed by rat liver after subtoxic exposure to acetaminophen

et al. 2021

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To identify changes in extracellular vesicles (EVs) secreted by the liver following druginduced liver injury (DILI), rats were treated with a subtoxic dose (500 mg/kg) of the analgesic drug, acetaminophen (APAP). EVs were collected by liver perfusion of sham and APAP-treated rats. Changes in EVs morphology were examined by transmission electron microscopic analysis of negatively stained vesicles. Results from morphometric analysis of EVs revealed striking differences in their size and distribution. Proteome composition of EVs collected by liver perfusion was determined by mass spectrometry using methods of sample preparation that enabled better detection of both highly hydrophobic proteins and proteins with complex post-translational modifications. The collection of EVs after liver perfusion is an approach that enables the isolation of EVs shed not only by isolated hepatocytes, but also by the entire complement of hepatic cells. EVs derived after DILI had a lower content of alpha-1-macroglobulin, ferritin, and members of cytochrome 450 family. Fibronectin, aminopeptidase N, metalloreductase STEAP4, integrin beta, and members of the annexin family were detected only in APAP-treated samples of EVs. These results show that the present approach can provide valuable insights into the response of the liver following drug-induced liver injury.

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Section: Proteins Detected Only In Evs Shed By Apap-treated Livermentioning

confidence: 99%

Changes in the proteome of extracellular vesicles shed by rat liver after subtoxic exposure to acetaminophen

et al. 2021

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“…Intriguingly, the knockout of exosomal TLN-2 in murine lymphocytes TK1 leads to a reduced binding to the integrin ligand ICAM-1 and MAdCAM-1. Furthermore, TLN-2-deficient T-cell-exosomes were less efficiently internalized by murine bEnd.3 endothelial cells, compared with control exosomes, suggesting a critical role of TLN-2 in integrin functions in exosomes [ 100 ]. An interesting evidence is the involvement of TLN and integrin in invadosomes [ 101 ], microdomains including podosomes and invadopodia formed at the ventral surface of the cells capable of interacting with ECM and degrading it [ 102 , 103 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding

Galardi

Colletti

Lavarello

et al. 2020

Cancers

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Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS group, respectively. Gene enrichment analysis of exclusively and differentially expressed proteins and network analysis identified in RBVS exosomes upregulated proteins specifically related to invasion and metastasis, such as proteins involved in extracellular matrix (ECM) remodeling and interaction, resistance to anoikis and the metabolism/catabolism of glucose and amino acids.

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“…Like other cellular integrins, the ability of those α4β7 integrins expressed on lymphocytes to bind ligand MAdCAM-1 is dynamically regulated by intracellular signaling cascades that culminate in the binding to the integrin cytoplasmic domain by an adaptor protein talin [7]. This dynamic and reversible binding of talin enables the versatile affinity regulation of integrins.…”

Section: Exosomoal Regulation Of Lymphocyte Homingmentioning

confidence: 99%

“…The absence of the intracellular signaling cascade due to the loss of a talin co-activator kindlin has been shown to generate non-adhesive leukocyte integrins, which has been observed in a primary immune deficiency known as leukocyte adhesion deficiency type III. Soe et al has shown that talin-2, one of two talin isoforms, is critical for the ability of the exosomal integrins α4β7 and αLβ2 to bind ligands [7]. Notably, these results have demonstrated that even within exosomes meas-uring~150 nm diameter, parts of the integrinsignaling cascades operate to support exosomal integrin activities [7].…”

Section: Exosomoal Regulation Of Lymphocyte Homingmentioning

confidence: 99%

“…Soe et al has shown that talin-2, one of two talin isoforms, is critical for the ability of the exosomal integrins α4β7 and αLβ2 to bind ligands [7]. Notably, these results have demonstrated that even within exosomes meas-uring~150 nm diameter, parts of the integrinsignaling cascades operate to support exosomal integrin activities [7].…”

Section: Exosomoal Regulation Of Lymphocyte Homingmentioning

confidence: 99%

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Targeted remodeling of breast cancer and immune cell homing niches by exosomal integrins

et al. 2020

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Exosomes represent an important subset of extracellular vesicles involved in inter-cellular communications in health and diseases. Exosomes secreted from cancer and immune cells travel to the specific tissues containing homing niches. The exosomes reaching the niches dynamically modify the gene expression and molecular architectures of the homing niche micro-environments. Cell adhesion molecule integrins regulate the tissue-specific homing patterns of not only cancer and immune cells, but also of the exosomes secreted from those cells. The exosomemediated remodeling of the homing niches would affect immune lymphocyte migration and host defense, as well as cancer metastasis, thereby representing a potential therapeutic target.

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Talin-2 regulates integrin functions in exosomes

Cited by 16 publications

References 33 publications

Changes in the proteome of extracellular vesicles shed by rat liver after subtoxic exposure to acetaminophen

Changes in the proteome of extracellular vesicles shed by rat liver after subtoxic exposure to acetaminophen

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding

Targeted remodeling of breast cancer and immune cell homing niches by exosomal integrins

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