Thy-3, a Developmentally Regulated T-Cell Glycoprotein Associated to Thy-1 in Detergent-Resistant Membrane Microdomains

Cell-cell contacts are essential for morphogenesis and tissue function and play a vital role in mediating endothelial cohesion within the vascular system during vessel growth and organization. We identified a novel junctional adhesion molecule, named JAM-2, by a selective RNA display method, which allowed identification of transcripts encoding immunoglobulin superfamily molecules regulated during coculture of endothelial cells with tumor cells. The JAM-2 transcript is highly expressed during embryogenesis and is detected in lymph node and Peyer's patches RNA of adult mice. Accordingly, antibodies specific for JAM-2 stain high endothelial venules and lymphatic vessels in lymphoid organs, and vascular structures in the kidney. Using real time video microscopy, we show that JAM-2 is localized within minutes to the newly formed cell-cell contact. The role of the protein in the sealing of cell-cell contact is further suggested by the reduced paracellular permeability of cell monolayer transfected with JAM-2 cDNA, and by the localization of JAM-2 to tight junctional complexes of polarized cells. Taken together, our results suggest that JAM-2 is a novel vascular molecule, which participates in interendothelial junctional complexes.

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Mechanism of Catecholamine-Mediated Destabilization of Messenger RNA Encoding Thy-1 Protein in T-Lineage Cells

Wajeman-Chao¹,

Lancaster²,

Graf

et al. 1998

The Journal of Immunology

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The Ig superfamily cell surface glycoprotein Thy-1 expressed on immune cells and neurons of rodents and humans is hypothesized to function in cell adhesion and signal transduction in T cell differentiation, proliferation, and apoptosis. This study analyzes effects of cAMP and catecholamines on transcriptional Thy-1 gene expression. Incubation of murine thymocytes or S49 mouse thymoma cells with dibutyryl-cAMP, 8-bromo-cAMP, cholera toxin, norepinephrine, or isoproterenol caused time- and concentration-dependent decreases in levels of Thy-1 mRNA assayed by Northern hybridization or T2 nuclease protection. After 4 h of treatment with 500 μM dibutyryl-cAMP or 8-bromo-cAMP, 1 nM cholera toxin, 100 μM norepinephrine, or 100 μM isoproterenol, Thy-1 mRNA levels were 60 to 96% lower than those of controls. Norepinephrine-mediated decreases in Thy-1 mRNA levels were prevented by the β-adrenergic receptor antagonist propranolol (10 μM). Dibutyryl-cAMP and norepinephrine decreased the apparent half-life of S49 cell Thy-1 mRNA from ≫6 h to 2 to 3 h, whereas nuclear run-on assays showed no cAMP or norepinephrine effect on de novo transcription of the Thy-1 gene. In mutant S49 cells lacking cAMP-dependent protein kinase A, neither dibutyryl cAMP nor norepinephrine affected Thy-1 mRNA levels. These observations show that exogenous cAMP and norepinephrine can induce decreases in steady state Thy-1 mRNA levels in T-lineage cells through posttranscriptional destabilization of Thy-1 mRNA, associated with protein kinase A-mediated protein phosphorylation. Catecholamine-mediated β-adrenergic protein kinase A-dependent Thy-1 mRNA destabilization may be an example of a more general mRNA decay system regulating cellular responses to stress.

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Thy-3, a Developmentally Regulated T-Cell Glycoprotein Associated to Thy-1 in Detergent-Resistant Membrane Microdomains

Cited by 3 publications

References 25 publications

The multiple roles of Thy-1 in cell differentiation and regeneration

The multiple roles of Thy-1 in cell differentiation and regeneration

JAM-2, a Novel Immunoglobulin Superfamily Molecule, Expressed by Endothelial and Lymphatic Cells

Mechanism of Catecholamine-Mediated Destabilization of Messenger RNA Encoding Thy-1 Protein in T-Lineage Cells

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