The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains

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.

Interaction of Syntenin-1 and the NG2 Proteoglycan in Migratory Oligodendrocyte Precursor Cells

“…8 and 18). Our results are similar to observations in T and B lymphocytes where a subpopulation of syntenin-1 colocalizes with the binding partner CD6 after capping (24). Like NG2, CD6 is a type I membrane glycoprotein expressed by thymocytes, by mature T and B lymphocytes, and in some neuronal subpopulations in basal ganglia and cerebellar cortex (29).…”

“…Both a membrane-associated and a cytosolic distribution of the protein were observed, similar to observations in lymphocytes (24). In both Oli-neu and primary cells, the intracellular staining at high resolution often appeared punctated and may represent vesicular association.…”

RETRACTED: mda-9/Syntenin Regulates the Metastatic Phenotype in Human Melanoma Cells by Activating Nuclear Factor-κB

“…mda-9, also called syntenin, is now recognized as a significant member of the expanding family of scaffolding proteins with highly potent and diverse biological activities (3,4). A noticeable feature of mda-9/ syntenin is the presence of tandem PDZ domains of 83 and 80 amino acid residues, respectively (PDZ1 and PDZ2), which selectively bind to specific motifs at the COOH termini of partner proteins, including class B ephrins, pro-transforming growth factor-a, PTP-D, phosphatidylinositol 4,5-biphosphate, neurofaschin, neurexin, schwannomin (also known as merlin), interleukin-5 receptor a, lymphocyte receptor CD63, various glutamate receptor subtypes, and the syndecan family of heparan sulfate proteoglycans (3,5,6). This flexibility of interacting partners allows MDA-9/syntenin to participate in an assortment of biological functions, including receptor clustering (7), protein trafficking (8,9), synaptic transmission (3), activation of the transcription factor Sox4 (10), syndecan recycling through endosomal compartments (5), and cytoskeleton-membrane organization (11,12).…”

Controlled initiation and quantitative visualization of cell interaction dynamics

“…Furthermore, CD6 has a long cytoplasmic tail that might be involved in the recruitment of signalling molecules (Kobarg et al, 1997). A potential candidate for this role is Syntenin-1, a molecule that interacts with CD6 (Gimferrer et al, 2005). Syntenin-1 has PDZ 5 domains, which are protein-interaction modules that can interact with phosphoinositide (PIP) molecules, which are, amongst others, involved in cytoskeleton remodelling (Zimmermann, 2006).…”

“…CD6 might perform its function via the binding of SLP-76, a positive regulator of T-cell activation, to the cytoplasmic tail of CD6 (Hassan et al, 2006). Another possibility for CD6 to exert its function is by its binding to Syntenin-1, a protein that can bind cytoskeletal proteins and signal transduction effectors (Gimferrer et al, 2005).…”