An MEK-cofilin signalling module controls migration of human T cells in 3D but not 2D environments
T cells infiltrate peripheral tissues to execute immunosurveillance and effector functions. For this purpose, T cells first migrate on the two-dimensional (2D) surface of endothelial cells to undergo transendothelial migration. Then they change their mode of movement to undergo migration within the...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
30 July 2010
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| In: |
The EMBO journal
Year: 2010, Volume: 29, Issue: 17, Pages: 2915-2929 |
| ISSN: | 1460-2075 |
| DOI: | 10.1038/emboj.2010.153 |
| Online Access: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1038/emboj.2010.153 Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.1038/emboj.2010.153 
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| Author Notes: | Martin Klemke, Elisabeth Kramer, Mathias H Konstandin, Guido H Wabnitz and Yvonne Samstag |
| Summary: | T cells infiltrate peripheral tissues to execute immunosurveillance and effector functions. For this purpose, T cells first migrate on the two-dimensional (2D) surface of endothelial cells to undergo transendothelial migration. Then they change their mode of movement to undergo migration within the three-dimensional (3D)-extracellular matrix of the infiltrated tissue. As yet, no molecular mechanisms are known, which control migration exclusively in either 2D or 3D environments. Here, we describe a signalling module that controls T-cell chemotaxis specifically in 3D environments. In chemotaxing T cells, Ras activity is spatially restricted to the lamellipodium. There, Ras initiates activation of MEK, which in turn inhibits LIM-kinase 1 activity, thereby allowing dephosphorylation of the F-actin-remodelling protein cofilin. Interference with this MEK-cofilin module by either inhibition of MEK or by knockdown of cofilin reduces speed and directionality of chemotactic migration in 3D-extracellular matrices, but not on 2D substrates. This MEK-cofilin module may have an important function in the tissue positioning of T cells during an immune response. |
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| Item Description: | Gesehen am 14.03.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1460-2075 |
| DOI: | 10.1038/emboj.2010.153 |