Syntenin-1 and ezrin proteins link activated leukocyte cell adhesion molecule to the actin cytoskeleton

Cicerone Tudor, Joost te Riet, Christina Eich, Rolf Harkes, Nick Smisdom, Jessica Bouhuijzen Wenger, Marcel Ameloot, Matthew Holt, Johannes S Kanger, Carl G Figdor, Alessandra Cambi, Vinod Subramaniam

    Research output: Contribution to JournalArticleAcademicpeer-review


    Activated leukocyte cell adhesion molecule (ALCAM) is a type I transmembrane protein member of the immunoglobulin superfamily of cell adhesion molecules. Involved in important pathophysiological processes such as the immune response, cancer metastasis, and neuronal development, ALCAM undergoes both homotypic interactions with other ALCAM molecules and heterotypic interactions with the surface receptor CD6 expressed at the T cell surface. Despite biochemical and biophysical evidence of a dynamic association between ALCAM and the actin cytoskeleton, no detailed information is available about how this association occurs at the molecular level. Here, we exploit a combination of complementary microscopy techniques, including FRET detected by fluorescence lifetime imaging microscopy and single-cell force spectroscopy, and we demonstrate the existence of a preformed ligand-independent supramolecular complex where ALCAM stably interacts with actin by binding to syntenin-1 and ezrin. Interaction with the ligand CD6 further enhances these multiple interactions. Altogether, our results propose a novel biophysical framework to understand the stabilizing role of the ALCAM supramolecular complex engaged to CD6 during dendritic cell-T cell interactions and provide novel information on the molecular players involved in the formation and signaling of the immunological synapse at the dendritic cell side.

    Original languageEnglish
    Pages (from-to)13445-60
    Number of pages16
    JournalJournal of Biological Chemistry
    Issue number19
    Publication statusPublished - 2014


    • Actin Cytoskeleton
    • Animals
    • Antigens, CD
    • Antigens, Differentiation, T-Lymphocyte
    • Cell Adhesion Molecules, Neuronal
    • Cell Communication
    • Cytoskeletal Proteins
    • Dendritic Cells
    • Fetal Proteins
    • Humans
    • K562 Cells
    • Mice
    • Protein Binding
    • Syntenins
    • T-Lymphocytes
    • Journal Article
    • Research Support, Non-U.S. Gov't


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