An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking
Summary: Response to multiple microenvironmental cues and resilience to mechanical stress are essential features of trafficking leukocytes. Here, we describe unexpected role of titin (TTN), the largest protein encoded by the human genome, in the regulation of mechanisms of lymphocyte trafficking. Hu...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723005272 |
| _version_ | 1797823331361095680 |
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| author | Lara Toffali Beatrice D’Ulivo Cinzia Giagulli Alessio Montresor Elena Zenaro Massimo Delledonne Marzia Rossato Barbara Iadarola Andrea Sbarbati Paolo Bernardi Gabriele Angelini Barbara Rossi Nicola Lopez Wolfgang A. Linke Andreas Unger Dario Di Silvestre Louise Benazzi Antonella De Palma Sara Motta Gabriela Constantin Pierluigi Mauri Carlo Laudanna |
| author_facet | Lara Toffali Beatrice D’Ulivo Cinzia Giagulli Alessio Montresor Elena Zenaro Massimo Delledonne Marzia Rossato Barbara Iadarola Andrea Sbarbati Paolo Bernardi Gabriele Angelini Barbara Rossi Nicola Lopez Wolfgang A. Linke Andreas Unger Dario Di Silvestre Louise Benazzi Antonella De Palma Sara Motta Gabriela Constantin Pierluigi Mauri Carlo Laudanna |
| author_sort | Lara Toffali |
| collection | DOAJ |
| description | Summary: Response to multiple microenvironmental cues and resilience to mechanical stress are essential features of trafficking leukocytes. Here, we describe unexpected role of titin (TTN), the largest protein encoded by the human genome, in the regulation of mechanisms of lymphocyte trafficking. Human T and B lymphocytes express five TTN isoforms, exhibiting cell-specific expression, distinct localization to plasma membrane microdomains, and different distribution to cytosolic versus nuclear compartments. In T lymphocytes, the LTTN1 isoform governs the morphogenesis of plasma membrane microvilli independently of ERM protein phosphorylation status, thus allowing selectin-mediated capturing and rolling adhesions. Likewise, LTTN1 controls chemokine-triggered integrin activation. Accordingly, LTTN1 mediates rho and rap small GTPases activation, but not actin polymerization. In contrast, chemotaxis is facilitated by LTTN1 degradation. Finally, LTTN1 controls resilience to passive cell deformation and ensures T lymphocyte survival in the blood stream. LTTN1 is, thus, a critical and versatile housekeeping regulator of T lymphocyte trafficking. |
| first_indexed | 2024-03-13T10:21:31Z |
| format | Article |
| id | doaj.art-170109d87daa42509161d0df15919a04 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T10:21:31Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-170109d87daa42509161d0df15919a042023-05-20T04:29:51ZengElsevierCell Reports2211-12472023-05-01425112516An isoform of the giant protein titin is a master regulator of human T lymphocyte traffickingLara Toffali0Beatrice D’Ulivo1Cinzia Giagulli2Alessio Montresor3Elena Zenaro4Massimo Delledonne5Marzia Rossato6Barbara Iadarola7Andrea Sbarbati8Paolo Bernardi9Gabriele Angelini10Barbara Rossi11Nicola Lopez12Wolfgang A. Linke13Andreas Unger14Dario Di Silvestre15Louise Benazzi16Antonella De Palma17Sara Motta18Gabriela Constantin19Pierluigi Mauri20Carlo Laudanna21Department of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Molecular and Translational Medicine, University of Brescia; 25123 Brescia, Lombardia, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, Italy; The Center for Biomedical Computing (CBMC), University of Verona; 37134 Verona, Veneto, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Biotechnology, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Biotechnology, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Biotechnology, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, ItalyInstitute of Physiology II, University of Muenster, and Heart Center, University Medicine; 37075 Göttingen, GermanyInstitute of Physiology II, University of Muenster, and Heart Center, University Medicine; 37075 Göttingen, GermanyInstitute of Biomedical Technologies (ITB) CNR; 20090 Milan, Lombardia, ItalyInstitute of Biomedical Technologies (ITB) CNR; 20090 Milan, Lombardia, ItalyInstitute of Biomedical Technologies (ITB) CNR; 20090 Milan, Lombardia, ItalyInstitute of Biomedical Technologies (ITB) CNR; 20090 Milan, Lombardia, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, Italy; The Center for Biomedical Computing (CBMC), University of Verona; 37134 Verona, Veneto, ItalyInstitute of Biomedical Technologies (ITB) CNR; 20090 Milan, Lombardia, ItalyDepartment of Medicine, Division of General Pathology, Laboratory of Cell Trafficking and Signal Transduction, University of Verona; 37134 Verona, Veneto, Italy; The Center for Biomedical Computing (CBMC), University of Verona; 37134 Verona, Veneto, Italy; Corresponding authorSummary: Response to multiple microenvironmental cues and resilience to mechanical stress are essential features of trafficking leukocytes. Here, we describe unexpected role of titin (TTN), the largest protein encoded by the human genome, in the regulation of mechanisms of lymphocyte trafficking. Human T and B lymphocytes express five TTN isoforms, exhibiting cell-specific expression, distinct localization to plasma membrane microdomains, and different distribution to cytosolic versus nuclear compartments. In T lymphocytes, the LTTN1 isoform governs the morphogenesis of plasma membrane microvilli independently of ERM protein phosphorylation status, thus allowing selectin-mediated capturing and rolling adhesions. Likewise, LTTN1 controls chemokine-triggered integrin activation. Accordingly, LTTN1 mediates rho and rap small GTPases activation, but not actin polymerization. In contrast, chemotaxis is facilitated by LTTN1 degradation. Finally, LTTN1 controls resilience to passive cell deformation and ensures T lymphocyte survival in the blood stream. LTTN1 is, thus, a critical and versatile housekeeping regulator of T lymphocyte trafficking.http://www.sciencedirect.com/science/article/pii/S2211124723005272CP: Immunology |
| spellingShingle | Lara Toffali Beatrice D’Ulivo Cinzia Giagulli Alessio Montresor Elena Zenaro Massimo Delledonne Marzia Rossato Barbara Iadarola Andrea Sbarbati Paolo Bernardi Gabriele Angelini Barbara Rossi Nicola Lopez Wolfgang A. Linke Andreas Unger Dario Di Silvestre Louise Benazzi Antonella De Palma Sara Motta Gabriela Constantin Pierluigi Mauri Carlo Laudanna An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking Cell Reports CP: Immunology |
| title | An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking |
| title_full | An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking |
| title_fullStr | An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking |
| title_full_unstemmed | An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking |
| title_short | An isoform of the giant protein titin is a master regulator of human T lymphocyte trafficking |
| title_sort | isoform of the giant protein titin is a master regulator of human t lymphocyte trafficking |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723005272 |
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