- Peptide (C)KELTKHYQGDNDTD, corresponding to amino acid residues 119 - 132 of mouse TSPAN18 (Accession Q80WR1). Extracellular, 2nd loop.
Tetraspanin 18 (extracellular) Blocking Peptide (#BLP-NR189)
- Western blot analysis of rat brain membranes (lanes 1 and 4), mouse brain membranes (lanes 2 and 5) and rat heart lysate (lanes 3 and 6):
- Western blot analysis of human THP-1 monocytic leukemia cell line lysates (lanes 1 and 4), human HUVEC endothelial cell line lysates (lanes 2 and 5) and mouse BV-2 microglia cell line lysate:1-3. Anti-Tetraspanin 18 (extracellular) Antibody (#ANR-189), (1:200).
4-6. Anti-Tetraspanin 18 (extracellular) Antibody, preincubated with Tetraspanin 18 (extracellular) Blocking Peptide (BLP-NR189).
- Expression of Tetraspanin 18 in mouse hippocampus.Immunohistochemical staining of perfusion-fixed frozen mouse brain sections with Anti-Tetraspanin 18 (extracellular) Antibody (#ANR-189), (1:300), followed by goat anti-rabbit-AlexaFluor-488. A. Staining in the mouse hippocampal dentate gyrus region, showed immunoreactivity (green) in the granule cell layer (G and an arrow) and in the hilus of the dentate gyrus (H). B. Pre-incubation of the antibody with Tetraspanin 18 (extracellular) Blocking Peptide (BLP-NR189), suppressed staining. Cell nuclei are stained with DAPI (blue). H = hilus, G = granule layer.
- Cell surface detection of Tetraspanin 18 by indirect flow cytometry in live intact mouse P815 mastocytoma cell line:___ Cells.
___ Cells + goat-anti-rabbit-PE.
___ Cells + Anti-Tetraspanin 18 (extracellular) Antibody (#ANR-189), (5μg) + goat-anti-rabbit-PE.
Tetraspanin-18, also known as TSPAN18 (TSN18), is a member of the Tetraspanins (Tspans) family of four-span transmembrane proteins. The TSPAN18 gene may be involved in the development of psychotic symptoms and contributes to clinical heterogeneity of schizophrenia1,2. Functional studies have shown that knockdown of Tspan18 leads to reduced endothelial cell migration, invasion and tube formation. Tspan18 has dynamic expression, regulates vascular development and maturation in the embryo with re-expression in adulthood during wound healing3.
Tetraspanins (Tspans) are known as plasma membrane “master organizers.” They form Tspan-enriched microdomains (TEMs or TERMs) through lateral association with one another and other membrane proteins. Tetraspanins are characterized by their four transmembrane domains, made up of two extracellular loops - one small extracellular loop (SEL or EC1) and one larger extracellular loop (LEL or EC2), a short intracellular loop, and two short intracellular tails1.
Vascular endothelial growth factor (VEGF) signaling is crucial for both vasculogenesis and angiogenesis. VEGF also regulates the Notch pathway and thus arterial–venous specification. Loss of Notch signaling leads to the loss of arterial markers, the gain of venous markers and an increase in vascular sprouting. Tetraspanin 18 (Tspan18) is a novel key regulator of angiogenesis. Tspan18 is one of 33 members of the tetraspanin family. Tetraspanins generate multimolecular complexes resulting in microdomains distinct from lipid rafts. Although tetraspanins typically lack ligands, the tetraspanin microdomains function as signaling complexes in the plasma membrane by interacting with many membrane proteins. Tspan18 is expressed in the blood vessels, and is required for proper angiogenesis, including vessel patterning, vessel stability and arterial–venous specification. Tspan18 signaling also regulates VEGF and Notch pathways and wound healing. Tspan18 deficiency has been shown to reduce VEGF, VEGFR2, Notch3 and EphrinB2, and increase EphB4, VEGFR3, Semaphorin3, Neuropilin and PlexinD1 expression3.
Tspan18 is a novel regulator of thrombo-inflammation, the interplay between thrombosis and inflammation, which causes acute organ damage in diseases such as ischemic stroke and venous thrombosis. The tetraspanin family regulates the trafficking, clustering, and membrane diffusion of specific partner proteins. Tspan18 partners with the store-operated Ca2+ entry channel Orai1 on endothelial cells. Orai1 appears to be expressed in all cells and is critical in health and disease. Orai1 mutations cause human immunodeficiency, resulting in chronic and often lethal infections. Orai1 is therefore a promising drug target in autoimmune and inflammatory diseases, and Orai1 inhibitors are currently in clinical trials. Orai1 trafficking to the cell surface is partially impaired in the absence of Tspan18, resulting in impaired Ca2+ signaling and the impaired release of the thrombo-inflammatory mediator von Willebrand factor following endothelial stimulation. Consequently, Tspan18-knockout mice are protected in ischemia-reperfusion and deep vein thrombosis models. Tspan18 is relatively highly expressed in endothelial cells, as demonstrated in analysis of publicly available single-cell transcriptomic data. Tspan18 is required for normal Ca2+ signaling in platelets, though the functional consequences are subtle and restricted to mildly defective platelet aggregation and spreading induced by the platelet collagen receptor GPVI. Tspan18 also regulates Orai1 Ca2+ channel function at the cell surface by promoting its clustering4.
Species reactivity key:
Anti-Tetraspanin 18 (extracellular) Antibody (#ANR-189) is a highly specific antibody directed against an extracellular epitope of the mouse protein. The antibody can be used in western blot, immunohistochemistry and flow cytometry applications. It has been designed to recognize TSPAN18 from mouse, rat and human samples.