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* Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742;
Leibniz Institute for Neurobiology, Magdeburg, Germany, and Friedrich-Schiller-University, Jena, Germany; and
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030
The BCR serves as both signal transducer and Ag transporter. Binding of Ags to the BCR induces signaling cascades and Ag processing and presentation, two essential cellular events for B cell activation. BCR-initiated signaling increases BCR-mediated Ag-processing efficiency by increasing the rate and specificity of Ag transport. Previous studies showed a critical role for the actin cytoskeleton in these two processes. In this study, we found that actin-binding protein 1 (Abp1/HIP-55/SH3P7) functioned as an actin-binding adaptor protein, coupling BCR signaling and Ag-processing pathways with the actin cytoskeleton. Gene knockout of Abp1 and overexpression of the Src homology 3 domain of Abp1 inhibited BCR-mediated Ag internalization, consequently reducing the rate of Ag transport to processing compartments and the efficiency of BCR-mediated Ag processing and presentation. BCR activation induced tyrosine phosphorylation of Abp1 and translocation of both Abp1 and dynamin 2 from the cytoplasm to plasma membrane, where they colocalized with the BCR and cortical F-actin. Mutations of the two tyrosine phosphorylation sites of Abp1 and depolymerization of the actin cytoskeleton interfered with BCR-induced Abp1 recruitment to the plasma membrane. The inhibitory effect of a dynamin proline-rich domain deletion mutant on the recruitment of Abp1 to the plasma membrane, coimmunoprecipitation of dynamin with Abp1, and coprecipitation of Abp1 with GST fusion of the dyanmin proline-rich domain demonstrate the interaction of Abp1 with dynamin 2. These results demonstrate that the BCR regulates the function of Abp1 by inducing Abp1 phosphorylation and actin cytoskeleton rearrangement, and that Abp1 facilitates BCR-mediated Ag processing by simultaneously interacting with dynamin and the actin cytoskeleton.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant AI059617 to W.S.
2 Address correspondence and reprint requests to Dr. Wenxia Song, Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742. E-mail address: wenxsong{at}umd.edu
3 Abbreviations used in this paper: Abp1, actin-binding protein 1; ABD, F-actin-binding domain; AF, Alexa Fluor; E
RFP, MHC class II I-E -chain peptide fused with red fluorescence protein; LAMP-1, lysosome-associated membrane protein 1; N-WASP, neural Wiskott-Aldrich syndrome protein; PRD, proline-rich domain; RFP, red fluorescence protein; SH3, Src homology 3; Tf, transferrin; wt, wild type.
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