Schwannomin Isoform-1 Interacts with Syntenin via PDZ Domains

Jannatipour, Mehrdad; Dion, Patrick A.; Khan, Saad; Jindal, Hitesh K.; Fan, Xueping; Laganière, Janet; Chishti, Athar H.; Rouleau, Guy

doi:10.1074/jbc.m105792200

Cited by 70 publications

(51 citation statements)

References 50 publications

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“…The expression of ERM proteins by oligodendrocytes has not been reported. Interestingly, immature Schwann cells express NG2 and also the ERM protein merlin/schwannomin, which is a reported binding partner of syntenin-1 (34).…”

Section: Discussionmentioning

confidence: 99%

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

Chatterjee

Stegmüller

Schätzle

et al. 2008

Journal of Biological Chemistry

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Migration of oligodendrocyte precursors along axons is a necessary prerequisite for myelination, but little is known about underlying mechanisms. NG2 is a large membrane proteoglycan implicated in oligodendrocyte migration. Here we show that a PDZ domain protein termed syntenin-1 interacts with NG2 and that syntenin-1 is necessary for normal rates of migration. The association of syntenin-1 with NG2, identified in a yeast twohybrid screen, was confirmed by colocalization of both proteins within processes of oligodendroglial precursor cells and by coimmunoprecipitation from cell extracts. Syntenin-1 also colocalizes with NG2 in "co-capping" assays, demonstrating a lateral association of both proteins in live oligodendrocytes. RNA interference-mediated down-regulation of syntenin-1 in glial cells results in a significant reduction of migration in vitro, as does the presence of polyclonal antibody against NG2. Thus syntenin plays a role in the migration of oligodendroglial precursors, and we suggest that NG2-syntenin-1 interactions contribute to this.The NG2 proteoglycan is a type I membrane protein that is expressed by a variety of immature cells of several embryonic tissue origins including glia, muscle progenitor cells, and pericytes (1). In the central nervous system, expression of NG2 was originally thought to specify oligodendroglial progenitor cells, but more recent data suggest that NG2-expressing cells encompass a wider range of immature glial cells in white and gray matter. These include glia that make synaptic-like contacts with neurons in the hippocampus and cerebellum (2) and glial cells specifically associated with the nodes of Ranvier (3). Interestingly, many NG2-positive cells are both proliferative and motile or exhibit local process motility (4, 5). Antibodies to the NG2 extracellular domain inhibit migration of oligodendroglial progenitor cells and immature Schwann cells in in vitro migration assays (5, 6), and NG2 also plays a role in cell spreading in melanoma tumors, which express melanoma chondroitin sulfate proteoglycan (MCSP), the human ortholog of NG2 (7). Identifying the intracellular NG2-interacting proteins should aid in elucidating the function of this multidomain protein in migratory cells of the oligodendrocyte lineage.The intracellular domain of NG2 consists of the C-terminal 76 amino acids and has the PDZ (postsynaptic density-95/discs large/zona occludens-1) binding motif QYWV, which can interact with PDZ domain-containing proteins (8). To define relevant intracellular partners of the glycoprotein, we carried out a yeast two-hybrid screen using the complete intracellular domain of NG2 as bait. One of the proteins that we identified is syntenin-1 (also termed MDA-9). Syntenin-1 is a widely expressed PDZ protein that is often overexpressed in highly migratory metastatic tumors including melanoma (9).Here we demonstrate that syntenin is expressed by primary oligodendrocytes and show functional studies using the oligodendroglial precursor cell line Oli-neu. We provide biochemical, mor...

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Section: Discussionmentioning

confidence: 99%

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

Chatterjee

Stegmüller

Schätzle

et al. 2008

Journal of Biological Chemistry

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“…In fact, we also detected the accumulation of syntenin at CD43 caps (data not shown). This is not surprising because it is known that syntenin-1 interacts with proteins binding to the actin cytoskeleton (27,28).…”

Section: Colocalization Studies Of Cd6 and Syntenin-1 In Human Lymphomentioning

confidence: 99%

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

Gimferrer

Ibáñez

Farnós

et al. 2005

The Journal of Immunology

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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.

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“…Merlin interacts with F-actin through actin binding sites within the FERM domain (Xu and Gutmann, 1998;Brault et al, 2001;James et al, 2001). In addition to actin, several other merlin interacting proteins have been identified, which include b-fodrin/bII-spectrin (Scoles et al, 1998;Neill and Crompton, 2001), SCHIP-1 (Goutebroze et al, 2000), NHE-RF (Murthy et al, 1998), b1-integrin (Obremski et al, 1998), CD44 (Sainio et al, 1997;Morrison et al, 2001), HRS (Scoles et al, 2000), RhoGDI (Maeda et al, 1999), syntenin (Jannatipour et al, 2001), paxillin (Fernandez-Valle et al, 2002) and RIb subunit of the cAMP-protein kinase A (Gronholm et al, 2003). Among these proteins, NHE-RF, CD44 and RhoGDI have been independently identified as ERM binding partners (Tsukita et al, 1994;Reczek et al, 1997;Takahashi et al, 1997), while HRS and syntenin appear to be specific for merlin.…”

Section: Introductionmentioning

confidence: 99%

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

et al. 2004

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Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by bilateral vestibular schwannomas and meningiomas. Merlin, the neurofibromatosis 2 tumor suppressor protein, is related to the ERM (ezrin, radixin, moesin) proteins and, like its family members, is thought to play a role in plasma membrane-cytoskeletal interactions. We report a novel protein as a merlin-specific binding partner that we have named magicin (merlin and Grb2 interacting cytoskeletal protein) and show that the two proteins interact in vitro and in vivo as well as colocalize beneath the plasma membrane. Magicin is a 24 kDa protein that is expressed in many cell lines and tissues. Magicin, similar to merlin, associates with the actin cytoskeleton as determined by cofractionation, immunofluorescence and electron microscopy. Analysis of the magicin sequence reveals binding motifs for the adaptor protein Grb2. Employing affinity binding, blot overlay and co-immunoprecipitation assays, we demonstrate an interaction between Grb2 and magicin. In addition, merlin is capable of forming a ternary complex with magicin and Grb2. These results support a role for merlin in receptor-mediated signaling at the cell surface, and may have implications in the regulation of cytoskeletal reorganization.

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Schwannomin Isoform-1 Interacts with Syntenin via PDZ Domains

Cited by 70 publications

References 50 publications

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

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

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

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

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