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

被引:44
作者
Frittoli, Emanuele [2 ]
Matteoli, Gianluca [1 ]
Palamidessi, Andrea [2 ]
Mazzini, Elise [1 ]
Maddaluno, Luigi [2 ]
Disanza, Andrea [2 ]
Yang, Changsong [4 ]
Svitkina, Tatyana [4 ]
Rescigno, Maria [1 ]
Scita, Giorgio [2 ,3 ]
机构
[1] European Inst Oncol, Dept Expt Oncol, IEO, Via Ripamonti 435, I-20141 Milan, Italy
[2] FIRC Inst Mol Oncol Fdn, IFOM, I-20139 Milan, Italy
[3] Univ Milan, Dipartimento Med Chirurg & Odontoiatria, I-20142 Milan, Italy
[4] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA
基金
欧洲研究理事会;
关键词
ALDRICH-SYNDROME PROTEIN; CONTACT HYPERSENSITIVITY; FILAMENT NUCLEATION; LANGERHANS CELLS; IN-VIVO; RECEPTOR; EXPRESSION; MOTILITY; DYNAMICS; DISTINCT;
D O I
10.1016/j.immuni.2011.07.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DCs) flexibly adapt to different micro-environments 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.
引用
收藏
页码:388 / 399
页数:12
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