Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells
T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction b...
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eLife Sciences Publications Ltd
2024-02-01
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| Online Access: | https://elifesciences.org/articles/91903 |
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| author | Chinky Shiu Chen Liu Tithi Mandal Parijat Biswas Md Asmaul Hoque Purbita Bandopadhyay Bishnu Prasad Sinha Jafar Sarif Ranit D'Rozario Deepak Kumar Sinha Bidisha Sinha Dipyaman Ganguly |
| author_facet | Chinky Shiu Chen Liu Tithi Mandal Parijat Biswas Md Asmaul Hoque Purbita Bandopadhyay Bishnu Prasad Sinha Jafar Sarif Ranit D'Rozario Deepak Kumar Sinha Bidisha Sinha Dipyaman Ganguly |
| author_sort | Chinky Shiu Chen Liu |
| collection | DOAJ |
| description | T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 plays any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension upon chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn, are crucial for the integrin LFA1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the ‘outside-in’ signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge. |
| first_indexed | 2024-03-07T22:35:44Z |
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| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-07T22:35:44Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-a14cba93ad6745c2a55f2c2957de8ef02024-02-23T15:14:06ZengeLife Sciences Publications LtdeLife2050-084X2024-02-011210.7554/eLife.91903Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cellsChinky Shiu Chen Liu0https://orcid.org/0000-0003-1073-692XTithi Mandal1https://orcid.org/0000-0003-1672-7880Parijat Biswas2https://orcid.org/0000-0003-2235-2384Md Asmaul Hoque3Purbita Bandopadhyay4Bishnu Prasad Sinha5Jafar Sarif6Ranit D'Rozario7Deepak Kumar Sinha8Bidisha Sinha9https://orcid.org/0000-0001-6449-8205Dipyaman Ganguly10https://orcid.org/0000-0002-7786-1795IICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, IndiaDepartment of Biological Sciences, Indian Association for Cultivation of Science, Kolkata, IndiaIICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India; Academy of Scientific and Innovative Research, Ghaziabad, IndiaIICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India; Academy of Scientific and Innovative Research, Ghaziabad, IndiaIICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India; Academy of Scientific and Innovative Research, Ghaziabad, IndiaIICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India; Academy of Scientific and Innovative Research, Ghaziabad, IndiaIICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, India; Academy of Scientific and Innovative Research, Ghaziabad, IndiaDepartment of Biological Sciences, Indian Association for Cultivation of Science, Kolkata, IndiaDepartment of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, IndiaIICB-Translational Research Unit of Excellence, CSIR-Indian Institute of Chemical Biology, Kolkata, IndiaT cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 plays any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension upon chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn, are crucial for the integrin LFA1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the ‘outside-in’ signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.https://elifesciences.org/articles/91903Piezo1human T cellschemotaxiscell migrationmechanosensingfocal adhesion kinase |
| spellingShingle | Chinky Shiu Chen Liu Tithi Mandal Parijat Biswas Md Asmaul Hoque Purbita Bandopadhyay Bishnu Prasad Sinha Jafar Sarif Ranit D'Rozario Deepak Kumar Sinha Bidisha Sinha Dipyaman Ganguly Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells eLife Piezo1 human T cells chemotaxis cell migration mechanosensing focal adhesion kinase |
| title | Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells |
| title_full | Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells |
| title_fullStr | Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells |
| title_full_unstemmed | Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells |
| title_short | Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells |
| title_sort | piezo1 mechanosensing regulates integrin dependent chemotactic migration in human t cells |
| topic | Piezo1 human T cells chemotaxis cell migration mechanosensing focal adhesion kinase |
| url | https://elifesciences.org/articles/91903 |
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