The Signaling Adaptor Eps8 Is an Essential Actin Capping Protein for Dendritic Cell Migration

SummaryDendritic cells (DCs) flexibly adapt to different microenvironments by using diverse migration strategies that are ultimately dependent on the dynamics and structural organization of the actin cytoskeleton. Here, we have shown that DCs require the actin capping activity of the signaling adaptor Eps8 to polarize and to form elongated migratory protrusions. DCs from Eps8-deficient mice are impaired in directional and chemotactic migration in 3D in vitro and are delayed in reaching the draining lymph node (DLN) in vivo after inflammatory challenge. Hence, Eps8-deficient mice are unable to mount a contact hypersensitivity response. We have also shown that the DC migratory defect is cell autonomous and that Eps8 is required for the proper architectural organization of the actin meshwork and dynamics of cell protrusions. Yet, Eps8 is not necessary for antigen uptake, processing, and presentation. Thus, we have identified Eps8 as a unique actin capping protein specifically required for DC migration.

Graphical AbstractFigure optionsDownload high-quality image (315 K)Download as PowerPoint slideHighlights
► In vitro and in vivo dendritic cell directional migration in 3D requires Eps8
► Eps8−/− mice fail to mount a contact hypersensitivity response
► Eps actin capping activity is essential for cell-autonomous DC migration
► The migration deficit of Eps8−/− DCs is the sole cause of impaired immunity