LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 36

Search options

  1. Article ; Online: Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers.

    Katsuta, Hiroki / Okuda, Satoru / Nagayama, Kazuaki / Machiyama, Hiroaki / Kidoaki, Satoru / Kato, Masashi / Sokabe, Masahiro / Miyata, Takaki / Hirata, Hiroaki

    iScience

    2023  Volume 26, Issue 3, Page(s) 106090

    Abstract: Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs ... ...

    Abstract Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs relies on actin crosslinking by α-actinin. Upon reduction of α-actinin-mediated crosslinks, the myosin II activity induced flows of actin filaments and myosin II along SFs, leading to a decrease in traction force exertion to ECM. The fluidized SFs maintained their cable integrity probably through enhanced actin polymerization throughout SFs. A computational modeling analysis suggested that lowering the density of actin crosslinks caused viscous slippage of actin filaments in SFs and, thereby, dissipated myosin-generated force transmitting along SFs. As a cellular scale outcome, α-actinin depletion attenuated the ECM-rigidity-dependent difference in cell migration speed, which suggested that α-actinin-modulated SF mechanics is involved in the cellular response to ECM rigidity.
    Language English
    Publishing date 2023-02-01
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106090
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers

    Hiroki Katsuta / Satoru Okuda / Kazuaki Nagayama / Hiroaki Machiyama / Satoru Kidoaki / Masashi Kato / Masahiro Sokabe / Takaki Miyata / Hiroaki Hirata

    iScience, Vol 26, Iss 3, Pp 106090- (2023)

    2023  

    Abstract: Summary: Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission ... ...

    Abstract Summary: Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs relies on actin crosslinking by α-actinin. Upon reduction of α-actinin-mediated crosslinks, the myosin II activity induced flows of actin filaments and myosin II along SFs, leading to a decrease in traction force exertion to ECM. The fluidized SFs maintained their cable integrity probably through enhanced actin polymerization throughout SFs. A computational modeling analysis suggested that lowering the density of actin crosslinks caused viscous slippage of actin filaments in SFs and, thereby, dissipated myosin-generated force transmitting along SFs. As a cellular scale outcome, α-actinin depletion attenuated the ECM-rigidity-dependent difference in cell migration speed, which suggested that α-actinin-modulated SF mechanics is involved in the cellular response to ECM rigidity.
    Keywords Biological sciences ; Cell biology ; Biophysics ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  3. Article: Molecular Imaging of PD-1 Unveils Unknown Characteristics of PD-1 Itself by Visualizing "PD-1 Microclusters".

    Nishi, Wataru / Wakamatsu, Ei / Machiyama, Hiroaki / Matsushima, Ryohei / Yoshida, Yosuke / Nishikawa, Tetsushi / Toyota, Hiroko / Furuhata, Masae / Nishijima, Hitoshi / Takeuchi, Arata / Suzuki, Makoto / Yokosuka, Tadashi

    Advances in experimental medicine and biology

    2024  Volume 1444, Page(s) 197–205

    Abstract: Programmed cell death-1 (PD-1) is one of the most famous coinhibitory receptors that are expressed on effector T cells to regulate their function. The PD-1 ligands, PD-L1 and PD-L2, are expressed by various cells throughout the body at steady state and ... ...

    Abstract Programmed cell death-1 (PD-1) is one of the most famous coinhibitory receptors that are expressed on effector T cells to regulate their function. The PD-1 ligands, PD-L1 and PD-L2, are expressed by various cells throughout the body at steady state and their expression was further regulated within different pathological conditions such as tumor-bearing and chronic inflammatory diseases. In recent years, immune checkpoint inhibitor (ICI) therapies with anti-PD-1 or anti-PD-L1 has become a standard treatment for various malignancies and has shown remarkable antitumor effects. Since the discovery of PD-1 in 1992, a huge number of studies have been conducted to elucidate the function of PD-1. Herein, this paper provides an overview of PD-1 biological findings and sheds some light on the current technology for molecular imaging of PD-1.
    MeSH term(s) Humans ; Programmed Cell Death 1 Receptor/metabolism ; Neoplasms/metabolism ; T-Lymphocytes/metabolism ; B7-H1 Antigen/metabolism ; Immunotherapy/methods ; Molecular Imaging
    Chemical Substances Programmed Cell Death 1 Receptor ; B7-H1 Antigen
    Language English
    Publishing date 2024-03-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 410187-X
    ISSN 0065-2598
    ISSN 0065-2598
    DOI 10.1007/978-981-99-9781-7_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article: Activation probability of a single naïve T cell upon TCR ligation is controlled by T cells interacting with the same antigen‐presenting cell

    Machiyama, Hiroaki / Yamaguchi, Tomoyuki / Watanabe, Tomonobu M. / Yanagida, Toshio / Fujita, Hideaki

    FEBS letters. 2021 June, v. 595, no. 11

    2021  

    Abstract: Accurate recognition of antigens by specific T cells is crucial for adaptive immunity to work properly. The activation of a T‐cell antigen‐specific response by an antigen‐presenting cell (APC) has not been clearly measured at a single T‐cell level. It is ...

    Abstract Accurate recognition of antigens by specific T cells is crucial for adaptive immunity to work properly. The activation of a T‐cell antigen‐specific response by an antigen‐presenting cell (APC) has not been clearly measured at a single T‐cell level. It is also unknown whether the cell‐extrinsic environment alters antigen recognition by a T cell. To measure the activation probability of a single T cell by an APC, we performed a single‐cell live imaging assay and found that the activation probability changes depending not only on the antigens but also on the interactions of other T cells with the APC. We found that the specific reactivity of single naïve T cells was poor. However, their antigen‐specific reactivity increased drastically when attached to an APC interacting with activated T cells. Activation of T cells was suppressed when regulatory T cells interacted with the APC. These findings suggest that although the ability of APCs to activate an antigen‐specific naïve T cell is low at a single‐cell level, the surrounding environment of APCs improves the specificity of the bulk response.
    Keywords T-lymphocytes ; adaptive immunity ; antigen-presenting cells ; antigens ; probability
    Language English
    Dates of publication 2021-06
    Size p. 1512-1524.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14082
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  5. Article ; Online: Activation probability of a single naïve T cell upon TCR ligation is controlled by T cells interacting with the same antigen-presenting cell.

    Machiyama, Hiroaki / Yamaguchi, Tomoyuki / Watanabe, Tomonobu M / Yanagida, Toshio / Fujita, Hideaki

    FEBS letters

    2021  Volume 595, Issue 11, Page(s) 1512–1524

    Abstract: Accurate recognition of antigens by specific T cells is crucial for adaptive immunity to work properly. The activation of a T-cell antigen-specific response by an antigen-presenting cell (APC) has not been clearly measured at a single T-cell level. It is ...

    Abstract Accurate recognition of antigens by specific T cells is crucial for adaptive immunity to work properly. The activation of a T-cell antigen-specific response by an antigen-presenting cell (APC) has not been clearly measured at a single T-cell level. It is also unknown whether the cell-extrinsic environment alters antigen recognition by a T cell. To measure the activation probability of a single T cell by an APC, we performed a single-cell live imaging assay and found that the activation probability changes depending not only on the antigens but also on the interactions of other T cells with the APC. We found that the specific reactivity of single naïve T cells was poor. However, their antigen-specific reactivity increased drastically when attached to an APC interacting with activated T cells. Activation of T cells was suppressed when regulatory T cells interacted with the APC. These findings suggest that although the ability of APCs to activate an antigen-specific naïve T cell is low at a single-cell level, the surrounding environment of APCs improves the specificity of the bulk response.
    MeSH term(s) Adaptive Immunity ; Animals ; Antigen Presentation ; Antigen-Presenting Cells/cytology ; Antigen-Presenting Cells/immunology ; Biological Assay ; Calcium/immunology ; Calcium/metabolism ; Coculture Techniques ; Humans ; Ion Transport ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Probability ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Single-Cell Analysis/methods ; Spleen/cytology ; Spleen/immunology ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Receptors, Antigen, T-Cell ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-04-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14082
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Evaluation of therapeutic PD-1 antibodies by an advanced single-molecule imaging system detecting human PD-1 microclusters.

    Nishi, Wataru / Wakamatsu, Ei / Machiyama, Hiroaki / Matsushima, Ryohei / Saito, Kensho / Yoshida, Yosuke / Nishikawa, Tetsushi / Takehara, Tomohiro / Toyota, Hiroko / Furuhata, Masae / Nishijima, Hitoshi / Takeuchi, Arata / Azuma, Miyuki / Suzuki, Makoto / Yokosuka, Tadashi

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3157

    Abstract: With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical trials into ... ...

    Abstract With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical trials into consideration, but without a standard method to evaluate them. Here we establish an advanced imaging system to visualize human PD-1 microclusters, in which a minimal T cell receptor (TCR) signaling unit co-localizes with the inhibitory co-receptor PD-1 in vitro. In these microclusters PD-1 dephosphorylates both the TCR/CD3 complex and its downstream signaling molecules via the recruitment of a phosphatase, SHP2, upon stimulation with the ligand hPD-L1. In this system, blocking antibodies for hPD-1-hPD-L1 binding inhibits hPD-1 microcluster formation, and each therapeutic antibody (pembrolizumab, nivolumab, durvalumab and atezolizumab) is characterized by a proprietary optimal concentration and combinatorial efficiency enhancement. We propose that our imaging system could digitally evaluate PD-1-mediated T cell suppression to evaluate their clinical usefulness and to develop the most suitable combinations among ICIs or between ICIs and conventional cancer treatments.
    MeSH term(s) Humans ; Programmed Cell Death 1 Receptor ; Single Molecule Imaging ; Nivolumab/pharmacology ; Nivolumab/therapeutic use ; Neoplasms/diagnostic imaging ; Neoplasms/drug therapy ; Receptors, Antigen, T-Cell ; B7-H1 Antigen/metabolism ; Immunotherapy/methods
    Chemical Substances Programmed Cell Death 1 Receptor ; Nivolumab (31YO63LBSN) ; Receptors, Antigen, T-Cell ; B7-H1 Antigen
    Language English
    Publishing date 2023-06-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-38512-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: PD-L2 suppresses T cell signaling via coinhibitory microcluster formation and SHP2 phosphatase recruitment.

    Takehara, Tomohiro / Wakamatsu, Ei / Machiyama, Hiroaki / Nishi, Wataru / Emoto, Katsura / Azuma, Miyuki / Soejima, Kenzo / Fukunaga, Koichi / Yokosuka, Tadashi

    Communications biology

    2021  Volume 4, Issue 1, Page(s) 581

    Abstract: The coinhibitory receptor, PD-1, is of major importance for the suppression of T cell activation in various types of immune responses. A high-resolution imaging study showed that PD-1 forms a coinhibitory signalosome, "PD-1 microcluster", with the ... ...

    Abstract The coinhibitory receptor, PD-1, is of major importance for the suppression of T cell activation in various types of immune responses. A high-resolution imaging study showed that PD-1 forms a coinhibitory signalosome, "PD-1 microcluster", with the phosphatase, SHP2, to dephosphorylate the TCR/CD3 complex and its downstream signaling molecules. Such a consecutive reaction entirely depended on PD-1-PD-L1/2 binding. PD-L2 is expressed on professional antigen-presenting cells and also on some tumor cells, which possibly explains the discrepant efficacy of immune checkpoint therapy for PD-L1-negative tumors. Here, we performed precise imaging analysis of PD-L2 forming PD-1-PD-L2 clusters associating with SHP2. PD-L2 could compete with PD-L1 for binding to PD-1, occupying the same space at TCR microclusters. The PD-1 microcluster formation was inhibited by certain mAbs with functional consequences. Thus, PD-1 microcluster formation provides a visible index for the effectiveness of anti-PD-1- or anti-PD-L1/2-mediated T cell suppression. PD-L2 may exert immune suppressive responses cooperatively with PD-L1 on the microcluster scale.
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cells, Cultured ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Programmed Cell Death 1 Ligand 2 Protein/genetics ; Programmed Cell Death 1 Ligand 2 Protein/metabolism ; Programmed Cell Death 1 Receptor/physiology ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism ; Signal Transduction
    Chemical Substances Pdcd1 protein, mouse ; Pdcd1lg2 protein, mouse ; Programmed Cell Death 1 Ligand 2 Protein ; Programmed Cell Death 1 Receptor ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48)
    Language English
    Publishing date 2021-05-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-021-02111-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Evaluation of therapeutic PD-1 antibodies by an advanced single-molecule imaging system detecting human PD-1 microclusters

    Wataru Nishi / Ei Wakamatsu / Hiroaki Machiyama / Ryohei Matsushima / Kensho Saito / Yosuke Yoshida / Tetsushi Nishikawa / Tomohiro Takehara / Hiroko Toyota / Masae Furuhata / Hitoshi Nishijima / Arata Takeuchi / Miyuki Azuma / Makoto Suzuki / Tadashi Yokosuka

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 16

    Abstract: Abstract With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical ... ...

    Abstract Abstract With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical trials into consideration, but without a standard method to evaluate them. Here we establish an advanced imaging system to visualize human PD-1 microclusters, in which a minimal T cell receptor (TCR) signaling unit co-localizes with the inhibitory co-receptor PD-1 in vitro. In these microclusters PD-1 dephosphorylates both the TCR/CD3 complex and its downstream signaling molecules via the recruitment of a phosphatase, SHP2, upon stimulation with the ligand hPD-L1. In this system, blocking antibodies for hPD-1-hPD-L1 binding inhibits hPD-1 microcluster formation, and each therapeutic antibody (pembrolizumab, nivolumab, durvalumab and atezolizumab) is characterized by a proprietary optimal concentration and combinatorial efficiency enhancement. We propose that our imaging system could digitally evaluate PD-1-mediated T cell suppression to evaluate their clinical usefulness and to develop the most suitable combinations among ICIs or between ICIs and conventional cancer treatments.
    Keywords Science ; Q
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  9. Article ; Online: PD-L2 suppresses T cell signaling via coinhibitory microcluster formation and SHP2 phosphatase recruitment

    Tomohiro Takehara / Ei Wakamatsu / Hiroaki Machiyama / Wataru Nishi / Katsura Emoto / Miyuki Azuma / Kenzo Soejima / Koichi Fukunaga / Tadashi Yokosuka

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 12

    Abstract: Takehara et al performed imaging analysis of microcluster formation between the PD-L1 and PD-L2, which are known to play a role in T cell activation in response to tumour cell signaling. Their analysis showed that the cluster formation inhibited T cell ... ...

    Abstract Takehara et al performed imaging analysis of microcluster formation between the PD-L1 and PD-L2, which are known to play a role in T cell activation in response to tumour cell signaling. Their analysis showed that the cluster formation inhibited T cell receptor signaling and could serve as a visual index for PD-L1/2-targeted cancer therapies.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  10. Article ; Online: A novel c-Src recruitment pathway from the cytosol to focal adhesions.

    Machiyama, Hiroaki / Yamaguchi, Tomoyuki / Watanabe, Tomonobu M / Fujita, Hideaki

    FEBS letters

    2017  Volume 591, Issue 13, Page(s) 1940–1946

    Abstract: The role of myristoylation in the localization and catalytic activity of Src at focal adhesions was investigated by live-cell imaging and site-directed mutagenesis. Although the majority of activated Src molecules are localized at focal adhesions, it is ... ...

    Abstract The role of myristoylation in the localization and catalytic activity of Src at focal adhesions was investigated by live-cell imaging and site-directed mutagenesis. Although the majority of activated Src molecules are localized at focal adhesions, it is unclear how activated Src molecules are recruited to focal adhesions. Because Src is activated at the cell membrane, translocation of Src to cell membranes is considered to be essential for its recruitment to focal adhesions. Membrane-targeting-deficient Src mutant SrcG2A localizes at focal adhesions, indicating direct recruitment of Src from cytosol to focal adhesions. Furthermore, directly recruited Src molecules are shown to enhance paxillin dynamics at focal adhesions. These results reveal that the regulation of Src activation and translocation is more complex than previously suggested.
    MeSH term(s) Cell Membrane/metabolism ; Cytosol/metabolism ; Focal Adhesion Kinase 1/metabolism ; Focal Adhesions/metabolism ; HeLa Cells ; Humans ; Mechanotransduction, Cellular ; Mutation ; Myristic Acid/metabolism ; Protein Transport ; src-Family Kinases/genetics ; src-Family Kinases/metabolism
    Chemical Substances Myristic Acid (0I3V7S25AW) ; CSK tyrosine-protein kinase (EC 2.7.10.2) ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; PTK2 protein, human (EC 2.7.10.2) ; src-Family Kinases (EC 2.7.10.2)
    Language English
    Publishing date 2017-07
    Publishing country England
    Document type Letter
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.12696
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top