Academic Journal
FMNL1 and mDia1 promote efficient T cell migration through complex environments via distinct mechanisms
| العنوان: | FMNL1 and mDia1 promote efficient T cell migration through complex environments via distinct mechanisms |
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| المؤلفون: | Ashton L. Sigler, Scott B. Thompson, Logan Ellwood-Digel, Adithan Kandasamy, Mary J. Michaels, Dean Thumkeo, Shuh Narumiya, Juan C. Del Alamo, Jordan Jacobelli |
| المصدر: | Frontiers in Immunology, Vol 15 (2024) |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | T cell, formins, cell migration, motility, FMNL1, mDia1, Immunologic diseases. Allergy, RC581-607 |
| الوصف: | Lymphocyte trafficking and migration through tissues is critical for adaptive immune function and, to perform their roles, T cells must be able to navigate through diverse tissue environments that present a range of mechanical challenges. T cells predominantly express two members of the formin family of actin effectors, Formin-like 1 (FMNL1) and mammalian diaphanous-related formin 1 (mDia1). While both FMNL1 and mDia1 have been studied individually, they have not been directly compared to determine functional differences in promoting T cell migration. Through in vivo analysis and the use of in vitro 2D and 3D model environments, we demonstrate that FMNL1 and mDia1 are both required for effective T cell migration, but they have different localization and roles in T cells, with specific environment-dependent functions. We found that mDia1 promotes general motility in 3D environments in conjunction with Myosin-II activity. We also show that, while mDia1 is almost entirely in the cytoplasmic compartment, a portion of FMNL1 physically associates with the nucleus. Furthermore, FMNL1 localizes to the rear of migrating T cells and contributes to efficient migration by promoting deformation of the rigid T cell nucleus in confined environments. Overall, our data indicates that while FMNL1 and mDia1 have similar mechanisms of actin polymerization, they have distinct roles in promoting T cell migration. This suggests that differential modulation of FMNL1 and mDia1 can be an attractive therapeutic route to fine-tune T cell migration behavior. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1467415/full; https://doaj.org/toc/1664-3224; https://doaj.org/article/8d8a242143d24c529f8431db63d56272 |
| DOI: | 10.3389/fimmu.2024.1467415 |
| الاتاحة: | https://doi.org/10.3389/fimmu.2024.1467415 https://doaj.org/article/8d8a242143d24c529f8431db63d56272 |
| رقم الانضمام: | edsbas.D65C1BA0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2024.1467415 |
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