Syntenin-1 and ezrin proteins link activated leukocyte cell adhesion molecule to the actin cytoskeleton
Publication year
2014Source
Journal of Biological Chemistry, 289, 19, (2014), pp. 13445-13460ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Tumorimmunology
Journal title
Journal of Biological Chemistry
Volume
vol. 289
Issue
iss. 19
Page start
p. 13445
Page end
p. 13460
Subject
Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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.
This item appears in the following Collection(s)
- Academic publications [202801]
- Electronic publications [100942]
- Faculty of Medical Sciences [80020]
- Open Access publications [69657]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.