Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration
Mast cell chemotaxis is essential for cell recruitment to target tissues, where these cells play an important role in adaptive and innate immunity. Stem cell factor (SCF) is a major chemoattractant for mast cells. SCF binds to the KIT receptor, thereby triggering tyrosine phosphorylation in the cyto...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01058/full |
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| author | Arnau Navinés-Ferrer Arnau Navinés-Ferrer Erola Ainsua-Enrich Erola Ainsua-Enrich Eva Serrano-Candelas Eva Serrano-Candelas Joan Sayós Margarita Martin Margarita Martin |
| author_facet | Arnau Navinés-Ferrer Arnau Navinés-Ferrer Erola Ainsua-Enrich Erola Ainsua-Enrich Eva Serrano-Candelas Eva Serrano-Candelas Joan Sayós Margarita Martin Margarita Martin |
| author_sort | Arnau Navinés-Ferrer |
| collection | DOAJ |
| description | Mast cell chemotaxis is essential for cell recruitment to target tissues, where these cells play an important role in adaptive and innate immunity. Stem cell factor (SCF) is a major chemoattractant for mast cells. SCF binds to the KIT receptor, thereby triggering tyrosine phosphorylation in the cytoplasmic domain and resulting in docking sites for SH2 domain-containing molecules, such as Lyn and Fyn, and the subsequent activation of the small GTPases Rac that are responsible for cytoskeletal reorganization and mast cell migration. In previous works we have reported the role of 3BP2, an adaptor molecule, in mast cells. 3BP2 silencing reduces FcεRI-dependent degranulation, by targeting Lyn and Syk phosphorylation, as well as SCF-dependent cell survival. This study examines its role in SCF-dependent migration and reveals that 3BP2 silencing in human mast cell line (LAD2) impairs cell migration due to SCF and IgE. In that context we found that 3BP2 silencing decreases Rac-2 and Cdc42 GTPase activity. Furthermore, we identified Myo1f, an unconventional type-I myosin, as a new partner for 3BP2. This protein, whose functions have been described as critical for neutrophil migration, remained elusive in mast cells. Myo1f is expressed in mast cells and colocalizes with cortical actin ring. Interestingly, Myo1f-3BP2 interaction is modulated by KIT signaling. Moreover, SCF dependent adhesion and migration through fibronectin is decreased after Myo1f silencing. Furthermore, Myo1f silencing leads to downregulation of β1 and β7 integrins on the mast cell membrane. Overall, Myo1f is a new 3BP2 ligand that connects the adaptor to actin cytoskeleton and both molecules are involved in SCF dependent mast cell migration. |
| first_indexed | 2024-12-12T07:22:55Z |
| format | Article |
| id | doaj.art-c25a27fab5d042a0b49148b1aa874f1f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T07:22:55Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c25a27fab5d042a0b49148b1aa874f1f2022-12-22T00:33:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01058444100Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell MigrationArnau Navinés-Ferrer0Arnau Navinés-Ferrer1Erola Ainsua-Enrich2Erola Ainsua-Enrich3Eva Serrano-Candelas4Eva Serrano-Candelas5Joan Sayós6Margarita Martin7Margarita Martin8Biochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Barcelona, Barcelona, SpainLaboratory of Clinic and Experimental Immunoallergy, IDIBAPS, Barcelona, SpainBiochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Barcelona, Barcelona, SpainLaboratory of Clinic and Experimental Immunoallergy, IDIBAPS, Barcelona, SpainBiochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Barcelona, Barcelona, SpainLaboratory of Clinic and Experimental Immunoallergy, IDIBAPS, Barcelona, SpainImmune Regulation and Immunotherapy Group, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Autonomous University of Barcelona, Barcelona, SpainBiochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Barcelona, Barcelona, SpainLaboratory of Clinic and Experimental Immunoallergy, IDIBAPS, Barcelona, SpainMast cell chemotaxis is essential for cell recruitment to target tissues, where these cells play an important role in adaptive and innate immunity. Stem cell factor (SCF) is a major chemoattractant for mast cells. SCF binds to the KIT receptor, thereby triggering tyrosine phosphorylation in the cytoplasmic domain and resulting in docking sites for SH2 domain-containing molecules, such as Lyn and Fyn, and the subsequent activation of the small GTPases Rac that are responsible for cytoskeletal reorganization and mast cell migration. In previous works we have reported the role of 3BP2, an adaptor molecule, in mast cells. 3BP2 silencing reduces FcεRI-dependent degranulation, by targeting Lyn and Syk phosphorylation, as well as SCF-dependent cell survival. This study examines its role in SCF-dependent migration and reveals that 3BP2 silencing in human mast cell line (LAD2) impairs cell migration due to SCF and IgE. In that context we found that 3BP2 silencing decreases Rac-2 and Cdc42 GTPase activity. Furthermore, we identified Myo1f, an unconventional type-I myosin, as a new partner for 3BP2. This protein, whose functions have been described as critical for neutrophil migration, remained elusive in mast cells. Myo1f is expressed in mast cells and colocalizes with cortical actin ring. Interestingly, Myo1f-3BP2 interaction is modulated by KIT signaling. Moreover, SCF dependent adhesion and migration through fibronectin is decreased after Myo1f silencing. Furthermore, Myo1f silencing leads to downregulation of β1 and β7 integrins on the mast cell membrane. Overall, Myo1f is a new 3BP2 ligand that connects the adaptor to actin cytoskeleton and both molecules are involved in SCF dependent mast cell migration.https://www.frontiersin.org/article/10.3389/fimmu.2019.01058/fulladaptor moleculesunconventional myosinsKIT signalingmast cellscell migration and adhesioncytoske leton |
| spellingShingle | Arnau Navinés-Ferrer Arnau Navinés-Ferrer Erola Ainsua-Enrich Erola Ainsua-Enrich Eva Serrano-Candelas Eva Serrano-Candelas Joan Sayós Margarita Martin Margarita Martin Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration Frontiers in Immunology adaptor molecules unconventional myosins KIT signaling mast cells cell migration and adhesion cytoske leton |
| title | Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration |
| title_full | Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration |
| title_fullStr | Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration |
| title_full_unstemmed | Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration |
| title_short | Myo1f, an Unconventional Long-Tailed Myosin, Is a New Partner for the Adaptor 3BP2 Involved in Mast Cell Migration |
| title_sort | myo1f an unconventional long tailed myosin is a new partner for the adaptor 3bp2 involved in mast cell migration |
| topic | adaptor molecules unconventional myosins KIT signaling mast cells cell migration and adhesion cytoske leton |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01058/full |
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