CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapse

Regina Tavano, Rita Lucia Contento, Sonia Jimenez Baranda, Marzia Soligo, Loretta Tuosto, Santos Manes, Antonella Viola

Research output: Contribution to journalArticle

Abstract

During 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 accumulation3-5. 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.

Original languageEnglish
Pages (from-to)1270-1276
Number of pages7
JournalNature Cell Biology
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 2006

ASJC Scopus subject areas

  • Cell Biology

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    Tavano, R., Contento, R. L., Baranda, S. J., Soligo, M., Tuosto, L., Manes, S., & Viola, A. (2006). CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapse. Nature Cell Biology, 8(11), 1270-1276. https://doi.org/10.1038/ncb1492