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Results for “Syntenin-1”

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9 recordsLinked to original sources
PubMed2006

Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63.

Tetraspanins are clustered in specific microdomains (named tetraspanin-enriched microdomains, or TERM) in the plasma membrane and regulate the functions of associated transmembrane receptors, including integrins and receptor tyrosine kinases. We have identified syntenin-1, a PDZ domain-containing protein, as a new component of TERM and show that syntenin-1 specifically interacts with the tetraspanin CD63. Detailed biochemical and heteronuclear magnetic resonance spectroscopy (NMR) studies have demonstrated that the interaction is mediated by the C-terminal cytoplasmic region of the tetraspanin and the PDZ domains of syntenin-1. Upon interaction, NMR chemical shift perturbations were predominantly localized to residues around the binding pocket of PDZ1, indicating a specific mode of recognition of the cytoplasmic tail of CD63. In addition, the C terminus of syntenin-1 has a stabilizing role in the CD63-syntenin-1 association, as deletion of the last 17 amino acids abolished the interaction. The CD63-syntenin-1 complex is abundant on the plasma membrane, and the elevated expression of the wild-type syntenin-1 slows down constitutive internalization of the tetraspanin. Furthermore, internalization of CD63 was completely blocked in cells expressing a syntenin-1 mutant lacking the first 100 amino acids. Previous results have shown that CD63 is internalized via AP-2-dependent mechanisms. Hence, our data indicate that syntenin-1 can counteract the AP-2-dependent internalization and identify this tandem PDZ protein as a new regulator of endocytosis.

Animals↗
PubMed2006

Organization of the presynaptic active zone by ERC2/CAST1-dependent clustering of the tandem PDZ protein syntenin-1.

Presynaptic active zones contain a cytoskeletal matrix called the CAZ, which is thought to play a critical role in the regulation of active zone formation and neurotransmitter release. Recent studies have identified several CAZ components, but little is known about how they contribute to the molecular organization of active zones. Here, we report a novel PDZ [postsynaptic density-95/Discs large/zona occludens-1] interaction between the CAZ protein ERC2/CAST1 and the tandem PDZ protein syntenin-1, which is known to associate with diverse synaptic proteins, including glutamate receptor subunits, SynCAM, and beta-neurexin. This interaction promotes the localization of syntenin-1 at presynaptic ERC2 clusters. In addition to the PDZ interaction, multimerization of both ERC2 and syntenin-1 mediates syntenin-1 clustering. These results suggest that ERC2 promotes presynaptic syntenin-1 clustering by two distinct mechanisms and that syntenin-1 may contribute to the molecular organization of active zones by linking ERC2 and other CAZ components to diverse syntenin-1-associated synaptic proteins.

Adaptor Proteins, Signal Transducing↗
PubMed2004

The neuronal glycine transporter 2 interacts with the PDZ domain protein syntenin-1.

The glycine transporter subtype 2 (GlyT2) is localized at glycinergic axon terminals where it mediates the re-uptake of glycine from the extracellular space. In this study, we used the yeast two-hybrid system to search for proteins that interact with the cytoplasmic carboxy terminal tail region of GlyT2. Screening of a rat brain cDNA library identified the PDZ domain protein syntenin-1 as an intracellular binding partner of GlyT2. In pull-down experiments, the interaction between GlyT2 and syntenin-1 was found to involve the C-terminal amino acid residues of GlyT2 and the PDZ2 domain of syntenin-1. Syntenin-1 is widely expressed in brain and co-localizes with GlyT2 in brainstem sections. Furthermore, syntenin-1 binds syntaxin 1A, which is known to regulate the plasma membrane insertion of GlyT2. Thus, syntenin-1 may be an in vivo binding partner of GlyT2 that regulates its trafficking and/or presynaptic localization in glycinergic neurons.

Amino Acid Sequence↗
PubMed2001

The neural cell recognition molecule neurofascin interacts with syntenin-1 but not with syntenin-2, both of which reveal self-associating activity.

Neurofascin belongs to the L1 subgroup of the immunoglobulin superfamily of cell adhesion molecules and is implicated in axonal growth and fasciculation. We used yeast two-hybrid screening to identify proteins that interact with neurofascin intracellularly and therefore might link it to trafficking, spatial targeting, or signaling pathways. Here, we demonstrate that rat syntenin-1, previously published as syntenin, mda-9, or TACIP18 in human, is a neurofascin-binding protein that exhibits a wide-spread tissue expression pattern with a relative maximum in brain. Syntenin-1 was found not to interact with other vertebrate members of the L1 subgroup such as L1 itself or NrCAM. We confirmed the specificity of the neurofascin-syntenin-1 interaction by ligand-overlay assay, surface plasmon resonance analysis, and colocalization of both proteins in heterologous cells. The COOH terminus of neurofascin was mapped to interact with the second PDZ domain of syntenin-1. Furthermore, we isolated syntenin-2 that may be expressed in two isoforms. Despite their high sequence similarity to syntenin-1, syntenin-2alpha, which interacts with neurexin I, and syntenin-2beta do not bind to neurofascin or several other transmembrane proteins that are binding partners of syntenin-1. Finally, we report that syntenin-1 and -2 both form homodimers and can interact with each other.

Amino Acid Sequence↗
PubMed2005

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

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 co-immunoprecipitation 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.

Amino Acid Sequence↗
PubMed2026

A guide to selecting high-performing antibodies for Syntenin-1 (O00560) for use in western blot, immunoprecipitation, and immunofluorescence.

Syntenin-1 is the Syndecan-binding protein 1 and a PDZ domain-containing adaptor protein that regulates diverse cellular processes through its interactions with transmembrane receptors, cytoskeletal components, and signaling molecules. Here we have characterized twelve Syntenin-1 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While the use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

Syntenins↗
PubMed2006

The prevalence and significance of PDZ domain-phosphoinositide interactions.

PDZ domains predominate in multi-cellular organisms. They are ubiquitous protein-interaction modules recognizing short peptide sequences generally situated at the C-terminal end of plasma membrane proteins. They contribute to the formation and spatial confinement of protein complexes and thereby play an essential role in the control of cell signaling. Recent studies indicate that PDZ domains can also interact with phosphoinositides (PIPs), signaling lipids with key-roles in receptor signal transduction, membrane trafficking, cytoskeleton remodeling and nuclear processes. In particular the PDZ domains of syntenin-1 and syntenin-2 bind to phosphatidylinositol 4, 5-bisphosphate (PIP2) with high-affinity. Syntenin-1/PIP2 interaction is important for receptor cargo recycling and syntenin-2 plays a role in the organization of nuclear PIP2. In addition, other lower-affinity PDZ domain/PIPs interactions are documented. Here, we summarize and discuss the present knowledge about the occurrence, the biochemistry and the biology of PDZ domain-lipid interactions.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions.

PDZ (Postsynaptic density protein, Disc large, Zona occludens) domains are protein-protein interaction modules that predominate in submembranous scaffolding proteins. Recently, we showed that the PDZ domains of syntenin-1 also interact with phosphatidylinositol 4,5-bisphosphate (PIP2) and that this interaction controls the recruitment of the protein to the plasma membrane. Here we evaluate the general importance of PIP2-PDZ domain interactions. We report that most PDZ proteins bind weakly to PIP2, but that syntenin-2, the closest homolog of syntenin-1, binds with high affinity to PIP2 via its PDZ domains. Surprisingly, these domains target syntenin-2 to nuclear PIP2 pools, in nuclear speckles and nucleoli. Targeting to these sites is abolished by treatments known to affect these PIP2 pools. Mutational and domain-swapping experiments indicate that high-affinity binding to PIP2 requires both PDZ domains of syntenin-2, but that its first PDZ domain contains the nuclear PIP2 targeting determinants. Depletion of syntenin-2 disrupts the nuclear speckles-PIP2 pattern and affects cell survival and cell division. These findings show that PIP2-PDZ domain interactions can directly contribute to subnuclear assembly processes.

Carrier Proteins↗
PubMed2006

PDZ domain-phosphoinositide interactions in cell-signaling.

Proteins containing PDZ domains function as scaffolds for the formation and spatial confinement of large signaling complexes. They play an important role in the establishment and maintenance of cell polarity and neuronal connectivity. Therefore, they are intensively studied in the context of neurobiology and cancer. It is well established that PDZ domains are protein-interaction modules recognizing short peptide sequences generally situated at the C-terminal end of transmembrane receptors. Yet, it is not clear how those interactions are regulated. Our recent studies revealed that PDZ domains can also interact with phosphoinositides (PIPs), signaling lipids with key-roles in receptor signal transduction, membrane trafficking, cytoskeleton remodeling, subcellular compartmentalization and nuclear processes. In particular, we established that the PDZ domains of syntenin-1 and syntenin-2 bind to phosphatidylinositol 4, 5-bisphosphate (PIP2) with high-affinity. Syntenin-1/PIP2 interaction is important for receptor cargo recycling and syntenin-2 plays a role in the organization of nuclear PIP2. Those study cases indicate that cellular phosphoinositides might function as essential regulators of PDZ proteins. Here, we summarize and discuss our present knowledge about the occurrence, the biochemistry and the functionality of PDZ domain-lipid interactions.

Adaptor Proteins, Signal Transducing↗