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An MEK-cofilin signalling module controls migration of human T cells in 3D but not 2D environments.

ABSTRACT: 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.

SUBMITTER: Klemke M

PROVIDER: S-EPMC2944044 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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An MEK-cofilin signalling module controls migration of human T cells in 3D but not 2D environments.

Klemke Martin M Kramer Elisabeth E Konstandin Mathias H MH Wabnitz Guido H GH Samstag Yvonne Y

The EMBO journal 20100730 17

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 ...[more]

PMID: 20676060

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Project description:Predicting motion is essential for many everyday life activities, e.g., in road traffic. Previous studies on motion prediction failed to find consistent results, which might be due to the use of very different stimulus material and behavioural tasks. Here, we directly tested the influence of task (detection, extrapolation) and stimulus features (visual vs. audiovisual and three-dimensional vs. non-three-dimensional) on temporal motion prediction in two psychophysical experiments. In both experiments a ball followed a trajectory toward the observer and temporarily disappeared behind an occluder. In audiovisual conditions a moving white noise (congruent or non-congruent to visual motion direction) was presented concurrently. In experiment 1 the ball reappeared on a predictable or a non-predictable trajectory and participants detected when the ball reappeared. In experiment 2 the ball did not reappear after occlusion and participants judged when the ball would reach a specified position at two possible distances from the occluder (extrapolation task). Both experiments were conducted in three-dimensional space (using stereoscopic screen and polarised glasses) and also without stereoscopic presentation. Participants benefitted from visually predictable trajectories and concurrent sounds during detection. Additionally, visual facilitation was more pronounced for non-3D stimulation during detection task. In contrast, for a more complex extrapolation task group mean results indicated that auditory information impaired motion prediction. However, a post hoc cross-validation procedure (split-half) revealed that participants varied in their ability to use sounds during motion extrapolation. Most participants selectively profited from either near or far extrapolation distances but were impaired for the other one. We propose that interindividual differences in extrapolation efficiency might be the mechanism governing this effect. Together, our results indicate that both a realistic experimental environment and subject-specific differences modulate the ability of audiovisual motion prediction and need to be considered in future research.

Dataset Information

An MEK-cofilin signalling module controls migration of human T cells in 3D but not 2D environments.

Publications

An MEK-cofilin signalling module controls migration of human T cells in 3D but not 2D environments.

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