The lymphocyte receptor CD6 interacts with syntenin-1, a scaffolding protein containing PDZ domains

Idoia Gimferrer, Anna Ibáñez, Montse Farnós, Maria Rosa Sarrias, Rafael Fenutría, Sandra Roselló, Pascale Zimmermann, Guido David, Jordi Vives, Carles Serra-Pagès, Francisco Lozano

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

CD6 is a type I membrane glycoprotein expressed on thymocytes, mature T and B1a lymphocytes, and CNS cells. CD6 binds to activated leukocyte cell adhesion molecule (CD166), and is considered as a costimulatory molecule involved in lymphocyte activation and thymocyte development. Accordingly, CD6 partially associates with the TCR/CD3 complex and colocalizes with it at the center of the mature immunological synapse (IS) on T lymphocytes. However, the signaling pathway used by CD6 is still mostly unknown. The yeast two-hybrid system has allowed us the identification of syntenin-1 as an interacting protein with the cytoplasmic tail of CD6. Syntenin-1 is a PDZ (postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1) domain-containing protein, which functions as an adaptor protein able to bind cytoskeletal proteins and signal transduction effectors. Mutational analyses showed that certain amino acids of the most C-terminal sequence of CD6 (-YDDISAA) and the two postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1 domains of syntenin-1 are relevant to the interaction. Further confirmation of the CD6-syntenin-1 interaction was obtained from pull-down and coimmunoprecipitation assays in mammalian cells. Image analyses also showed that syntenin-1 accumulates at CD6 caps and at the IS. Therefore, we propose that syntenin-1 may function as a scaffolding protein coupling CD6 and most likely other lymphocyte receptors to cytoskeleton and/or signaling effectors during IS maturation.

Original languageEnglish
Pages (from-to)1406-1414
Number of pages9
JournalJournal of Immunology
Volume175
Issue number3
DOIs
StatePublished - 1 Aug 2005
Externally publishedYes

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