Nature Cell Biology
- 8, 1270 - 1276 (2006)
Published online: 22 October 2006; | doi:10.1038/ncb1492
CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapseRegina Tavano1, 5, Rita Lucia Contento1, 5, Sonia Jimenez Baranda2, Marzia Soligo3, Loretta Tuosto3, Santos Manes2 & Antonella Viola1, 41
Venetian Institute of Molecular Medicine, Department of Biomedical Science, University of Padua, 35100 Padua, Italy. 2
Department of Immunology and Oncology, Centro Nacional de Biotecnologia, 28049 Madrid, Spain. 3
Department of Cellular and Developmental Biology, University of Rome 'La Sapienza', 00185 Rome, Italy. 4
Istituto Clinico Humanitas, 20089 Rozzano (MI), Italy. 5
These authors contributed equally to this work.
Correspondence should be addressed to Antonella Viola antonella.viola@unipd.it FLNaLckCdc42CD3CD71During physiological T-cell stimulation by antigen presenting cells (APCs), a major T-cell membrane rearrangement is known to occur leading to the organization of 'supramolecular activation clusters' at the immunological synapse1,
2. A possible role for the synapse is the generation of membrane compartments where signalling may be organized and propagated2. Thus, engagement of the costimulatory molecule CD28 at the immunological synapse promotes the organization of a signalling compartment by inducing cytoskeletal changes and lipid raft accumulation3,
4,
5. We identified the actin-binding protein Filamin-A (FLNa) as a novel molecular partner of CD28. We found that, after physiological stimulation, CD28 associated with and recruited FLNa into the immunological synapse, where FLNa organized CD28 signalling. FLNa knockdown by short interfering RNA (siRNA) inhibited CD28-mediated raft accumulation at the immunological synapse and T-cell costimulation. Together, our data indicate that CD28 binding to FLNa is required to induce the T-cell cytoskeletal rearrangements leading to recruitment of lipid microdomains and signalling mediators into the immunological synapse.
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