title: The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration.
abstract: Dendritic 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.
authors.affiliation: IFOM, FIRC Institute of Molecular Oncology Foundation at IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Frittoli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Matteoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Palamidessi
authors.forename: Elisa
authors.initials: E
authors.lastname: Mazzini
authors.forename: Luigi
authors.initials: L
authors.lastname: Maddaluno
authors.forename: Andrea
authors.initials: A
authors.lastname: Disanza
authors.forename: Changsong
authors.initials: C
authors.lastname: Yang
authors.forename: Tatyana
authors.initials: T
authors.lastname: Svitkina
authors.forename: Maria
authors.initials: M
authors.lastname: Rescigno
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scita
mesh_terms: D051344:Actin Capping Proteins / Q000276:immunology*; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C513734:Abi1 protein, mouse; D051344:Actin Capping Proteins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins