Atypical cofilin signaling drives dendritic cell migration through the extracellular matrix via nuclear deformation
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To mount an adaptive immune response, dendritic cells must migrate to lymph nodes to present antigens to T cells. Critical to 3D migration is the nucleus, which is the size-limiting barrier for migration through the extracellular matrix. Here, we show that inflammatory activation of dendritic cells leads to the nucleus becoming spherically deformed and enables dendritic cells to overcome the typical 2- to 3-μm diameter limit for 3D migration through gaps in the extracellular matrix. We show that the nuclear shape change is partially attained through reduced cell adhesion, whereas improved 3D migration is achieved through reprogramming of the actin cytoskeleton. Specifically, our data point to a model whereby the phosphorylation of cofilin-1 at serine 41 drives the assembly of a cofilin-actomyosin ring proximal to the nucleus and enhances migration through 3D collagen gels. In summary, these data describe signaling events through which dendritic cells deform their nucleus and enhance their migratory capacity.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 113866 |
| Tidsskrift | Cell Reports |
| Vol/bind | 43 |
| Udgave nummer | 3 |
| Antal sider | 28 |
| ISSN | 2211-1247 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
We are thankful to P. Grijpstra for technical support throughout the project. We are also grateful to F. Stempels for advice regarding FLIM observations. G.v.d. Bogaart is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research innovation program (grant agreement 862137 ) and ZonMw (project grant 09120011910001 ). The proteomics experiments performed in this project and G.F.’s salary were funded by the European Union’s Horizon 2020 research and innovation program under grant agreement EPIC-XS-823839 . Work at the NNF CPR is funded by a donation from the NNF ( NNF14CC0001 ). C.K. is funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 861389 . L.Q.C. is supported by grant 11618 from the Dutch Cancer Society . W.H.R. is supported by a FOM projectruimte grant.
Funding Information:
We are thankful to P. Grijpstra for technical support throughout the project. We are also grateful to F. Stempels for advice regarding FLIM observations. G.v.d. Bogaart is supported by the European Research Council (ERC) under the European Union's Horizon 2020 research innovation program (grant agreement 862137) and ZonMw (project grant 09120011910001). The proteomics experiments performed in this project and G.F.’s salary were funded by the European Union's Horizon 2020 research and innovation program under grant agreement EPIC-XS-823839. Work at the NNF CPR is funded by a donation from the NNF (NNF14CC0001). C.K. is funded by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement 861389. L.Q.C. is supported by grant 11618 from the Dutch Cancer Society. W.H.R. is supported by a FOM projectruimte grant. H.W. and G.v.d. Bogaart designed the project and wrote the manuscript. H.W. performed the majority of the experiments. G.F. C.K. and J.V.O. planned, carried out, and analyzed the proteomic and phosphoproteomic experiments. G.v.d. Borg and W.H.R. planned, carried out, and analyzed the AFM experiments. L.Q.C. and R.C. carried out 3D collagen migration assays. N.v.H. and H.J.R. planned, carried out, and analyzed molecular modeling experiments. B.C. F.F. R.d.B. S. Maassen. M.V.B. S. Mahajan, D.D. and F.B. carried out experiments. The authors declare no competing interests.
Publisher Copyright:
© 2024 The Author(s)
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