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Vol. 18, Issue 9, 3451-3462, September 2007

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Syk-dependent Actin Dynamics Regulate Endocytic Trafficking and Processing of Antigens Internalized through the B-Cell Receptor

Delphine Le Roux^*, Danielle Lankar^*, Maria-Isabel Yuseff^*, Fulvia Vascotto^*, Takeaki Yokozeki, Gabrielle Faure-André^*, Evelyne Mougneau, Nicolas Glaichenhaus, Bénédicte Manoury^*, Christian Bonnerot^*,, and Ana-Maria Lennon-Duménil^*

*Institut National de la Santé et de la Recherche Médicale U653, Institut Curie, 75005, Paris, France; Department of Biochemistry, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, Japan 305-8577; and Institut National de la Santé et de la Recherche Médicale E0344, Université de Nice-Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, 06560 Valbonne, France

Submitted December 15, 2006; Revised June 15, 2007; Accepted June 18, 2007
Monitoring Editor: Sandra Schmid

Antigen binding to the B-cell receptor (BCR) induces multiple signaling cascades that ultimately lead to B lymphocyte activation. In addition, the BCR regulates the key trafficking events that allow the antigen to reach endocytic compartments devoted to antigen processing, i.e., that are enriched for major histocompatibility factor class II (MHC II) and accessory molecules such as H2-DM. Here, we analyze the role in antigen processing and presentation of the tyrosine kinase Syk, which is activated upon BCR engagement. We show that convergence of MHC II- and H2-DM–containing compartments with the vesicles that transport BCR-uptaken antigens is impaired in cells lacking Syk activity. This defect in endocytic trafficking compromises the ability of Syk-deficient cells to form MHC II-peptide complexes from BCR-internalized antigens. Altered endocytic trafficking is associated to a failure of Syk-deficient cells to properly reorganize their actin cytoskeleton in response to BCR engagement. We propose that, by modulating the actin dynamics induced upon BCR stimulation, Syk regulates the positioning and transport of the vesicles that carry the molecules required for antigen processing and presentation.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Deceased.

Address correspondence to: Ana-Maria Lennon-Duménil (Ana-Maria.Lennon{at}curie.fr).

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