NAG-2, a Novel Transmembrane-4 Superfamily (TM4SF) Protein That Complexes with Integrins and Other TM4SF Proteins

Tachibana, Isao; Bodorova, Jana; Berditchevski, Fedor; Zutter, Mary M.; Hemler, Martin E.

doi:10.1074/jbc.272.46.29181

Cited by 85 publications

(61 citation statements)

References 52 publications

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“…The present study, for the first time, screened multiple SCLC cell lines for tetraspanin expressions. All tetraspanins tested in this study (CD9, CD63, CD81, CD82, CD151, and NAG-2) are present in multiple organs including the lung (Nagira et al, 1994;Fitter et al, 1995;Oritani et al, 1996;Tachibana et al, 1997;Lantuejoul et al, 1998). The flow cytometry data indicated that, among these molecules, expressions of CD9 and NAG-2 were less frequent in SCLC compared with NSCLC.…”

Section: Discussionmentioning

confidence: 86%

“…M38 and M104, mouse MoAbs against CD81 and CD82, respectively, were gifts from Dr O Yoshie (Kinki University School of Medicine, Osaka, Japan). 6H1, 5C11, and NAG-1, mouse MoAbs against CD63, CD151, and NAG-2, respectively, and A1A5 and SG/19, mouse anti-b1 integrin MoAbs, were previously described (Tachibana et al, 1996;Berditchevski et al, 1997;Tachibana et al, 1997;Yauch et al, 1998). A mouse anti-N-CAM MoAb, ITK-2, was established in our laboratory and characterized previously (Saito et al, 1991).…”

Section: Antibodiesmentioning

confidence: 99%

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Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer

et al. 2003

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Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with nonsmall cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that downregulation of several members of tetraspanins is associated with progression of solid tumors, thus indicating poor prognosis. Here we screened 30 lung cancer cell lines for expression of tetraspanins, CD9, CD63, CD81, CD82, CD151, and NAG-2. Flow cytometry revealed that, among these proteins, CD9 is broadly expressed in NSCLC lines, but is absent or highly reduced in most SCLC lines (Po0.0001). Using the Boyden chamber and videomicroscopic cell motility assays, we showed that stable transfection of CD9 into an SCLC line, OS3-R5, reduced cell motility on fibronectin. Furthermore, by transient transfection of green fluorescent protein (GFP)-tagged CD9 into three other SCLC lines, we observed that SCLC cells expressing GFP-CD9 were uniformly less motile than untransfected cells. CD9 or GFP-CD9 was associated with b1 integrins and distributed at the tumor cell periphery and cell-cell contacts, suggesting that CD9 modifies b1 integrin function to reduce motility. These findings suggest that low expression of CD9 may contribute to the highly invasive and metastatic phenotype of SCLC.

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Section: Discussionmentioning

confidence: 86%

Section: Antibodiesmentioning

confidence: 99%

Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer

et al. 2003

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“…CD53 is restricted to leukocytes [55] and is absent from platelets [56, 57], so its expression does not appear to overlap with Tspan9. Tspan4 appears to be more widely expressed [58] but not by platelets [56, 57]. These expression profiles could explain how a platelet phenotype has been identified in the Tspan9-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

et al. 2016

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The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels. A GPVI activation defect was suggested by partially impaired GPVI-induced protein tyrosine phosphorylation. In mechanistic experiments, Tspan9 and GPVI co-immunoprecipitated and co-localised, but super-resolution imaging revealed no defects in collagen-induced GPVI clustering on Tspan9-deficient platelets. However, single particle tracking using total internal reflection fluorescence microscopy showed that GPVI lateral diffusion was reduced by approximately 50% in the absence of Tspan9. Therefore, Tspan9 plays a fine-tuning role in platelet activation by regulating GPVI membrane dynamics.

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“…Members of this family tend to associate both with each other, and with cell-type-specific partner proteins. For example, CD81 associates in B cells with CD19 (25) whereas in T cells it associates with CD4 and CD8 (26)(27)(28). Tetraspanins and their partners assemble in the membrane in tetraspaninenriched microdomains (TEMs), which facilitate key cellular functions.…”

Section: A Ctivation Of Naïve T Cells Requires Two Independent Signalsmentioning

confidence: 99%

Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

Sagi¹,

Landrigan

Levy³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Cluster of differentiation 81 (CD81) is a widely expressed tetraspanin molecule that physically associates with CD4 and CD8 on the surface of human T cells. Coengagement of CD81 and CD3 results in the activation and proliferation of T cells. CD81 also costimulated mouse T cells that lack CD28, suggesting either a redundant or a different mechanism of action. Here we show that CD81 and CD28 have a preference for different subsets of T cells: Primary human naïve T cells are better costimulated by CD81, whereas the memory T-cell subsets and Tregs are better costimulated by CD28. The more efficient activation of naïve T cells by CD81 was due to prolonged signal transduction compared with that by CD28. We found that IL-6 played a role in the activation of the naïve T-cell subset by CD81. Combined costimulation through both CD28 and CD81 resulted in an additive effect on Tcell activation. Thus, these two costimulatory molecules complement each other both in the strength of signal transduction and in T-cell subset inclusions. Costimulation via CD81 might be useful for expansion of T cells for adoptive immunotherapy to allow the inclusion of naïve T cells with their broad repertoire.

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NAG-2, a Novel Transmembrane-4 Superfamily (TM4SF) Protein That Complexes with Integrins and Other TM4SF Proteins

Cited by 85 publications

References 52 publications

Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer

Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer

Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

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