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Title: Syntenin-1 and Ezrin Proteins Link Activated Leukocyte Cell Adhesion Molecule to the Actin Cytoskeleton
Authors: Tudor, Cicerone
te Riet, Joost
Eich, Christina
Harkes, Rolf
Wenger, Jessica Bouhuijzen
AMELOOT, Marcel 
Holt, Matthew
Kanger, Johannes S.
Figdor, Carl G.
Cambi, Alessandra
Subramaniam, Vinod
Issue Date: 2014
Source: JOURNAL OF BIOLOGICAL CHEMISTRY, 289 (19), p. 13445-13460
Abstract: 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.
Notes: Cambi, A (reprint author), Univ Twente, MIRA Inst Biomed Technol & Tech Med, POB 217, NL-7500 AE Enschede, Netherlands;
Keywords: actin; atomic force microscopy; cell adhesion; cytoskeleton; Fluorescence Resonance Energy Transfer (FRET); ALCAM; FRET-FLIM; single-cell force spectroscopy
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ISSN: 0021-9258
e-ISSN: 1083-351X
DOI: 10.1074/jbc.M113.546754
ISI #: 000335522800042
Category: A1
Type: Journal Contribution
Validations: ecoom 2015
Appears in Collections:Research publications

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