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LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation.

Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT, Daneman R - J. Cell Biol. (2015)

Bottom Line: One important BBB property is the formation of a paracellular barrier made by tight junctions (TJs) between CNS endothelial cells (ECs).Here, we show that Lipolysis-stimulated lipoprotein receptor (LSR), a component of paracellular junctions at points in which three cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other nonneural tissues.We demonstrate that LSR is specifically expressed at tricellular junctions and that its expression correlates with the onset of BBB formation during embryogenesis.

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Affiliation: Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 fsohet@ucsd.edu rdaneman@ucsd.edu.

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LSR expression in adult mice. (A) Tissue sections of brain, lung, liver, and intestine were colabeled with antibodies directed against LSR (red) and CD31 (green, to label blood vessels). Expression of LSR in CD31+ ECs is only observed in the brain. Bar, 100 µm. (B) Tissue sections from adult mice were labeled with the blood vessel marker BSL I (green), and antibodies against occludin (blue, bicellular TJ) and LSR (red). The merged image indicates that in CNS blood vessels LSR is localized at the tricellular TJ where two bicellular TJ meet. Bar, 5 µm. (C, left) Quantitative real-time PCR analysis of LSR isoforms from purified brain ECs and liver ECs. Analysis indicates no detectable LSR expression in liver ECs but high expression of the α′ variant followed by α and β variants in brain ECs. (C, middle and right) Quantitative real-time PCR analysis of LSR variants from whole brain, lung, and liver. The expression in liver is much higher than brain or lung, and thus was given its own y axis (right). Splice variant composition is similar between brain and liver (α’ variant followed by α and β variants) but different in the lung (β variant followed by α’ and α variants). Data represent means ± SD (error bars) from three indipendent experiments. (D) Western blot profile of LSR from purified brain capillaries shows a stronger band for the α′ splice variant followed by α and β.
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fig1: LSR expression in adult mice. (A) Tissue sections of brain, lung, liver, and intestine were colabeled with antibodies directed against LSR (red) and CD31 (green, to label blood vessels). Expression of LSR in CD31+ ECs is only observed in the brain. Bar, 100 µm. (B) Tissue sections from adult mice were labeled with the blood vessel marker BSL I (green), and antibodies against occludin (blue, bicellular TJ) and LSR (red). The merged image indicates that in CNS blood vessels LSR is localized at the tricellular TJ where two bicellular TJ meet. Bar, 5 µm. (C, left) Quantitative real-time PCR analysis of LSR isoforms from purified brain ECs and liver ECs. Analysis indicates no detectable LSR expression in liver ECs but high expression of the α′ variant followed by α and β variants in brain ECs. (C, middle and right) Quantitative real-time PCR analysis of LSR variants from whole brain, lung, and liver. The expression in liver is much higher than brain or lung, and thus was given its own y axis (right). Splice variant composition is similar between brain and liver (α’ variant followed by α and β variants) but different in the lung (β variant followed by α’ and α variants). Data represent means ± SD (error bars) from three indipendent experiments. (D) Western blot profile of LSR from purified brain capillaries shows a stronger band for the α′ splice variant followed by α and β.

Mentions: We first examined LSR expression in different organs by immunostaining tissue sections of brain, liver, lung, and intestine for LSR and double-labeling for ECs with an antibody directed against CD31 (Fig. 1 A). In each of these organs there is robust LSR expression. However, LSR expression only colocalizes with CD31+ ECs in the brain and not in the peripheral organs. In the peripheral tissues, LSR staining is restricted to epithelial cells (lung, intestine) or hepatocytes (liver). These results confirm that Lsr is highly enriched in brain ECs compared with liver, lung, and intestinal ECs.


LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation.

Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT, Daneman R - J. Cell Biol. (2015)

LSR expression in adult mice. (A) Tissue sections of brain, lung, liver, and intestine were colabeled with antibodies directed against LSR (red) and CD31 (green, to label blood vessels). Expression of LSR in CD31+ ECs is only observed in the brain. Bar, 100 µm. (B) Tissue sections from adult mice were labeled with the blood vessel marker BSL I (green), and antibodies against occludin (blue, bicellular TJ) and LSR (red). The merged image indicates that in CNS blood vessels LSR is localized at the tricellular TJ where two bicellular TJ meet. Bar, 5 µm. (C, left) Quantitative real-time PCR analysis of LSR isoforms from purified brain ECs and liver ECs. Analysis indicates no detectable LSR expression in liver ECs but high expression of the α′ variant followed by α and β variants in brain ECs. (C, middle and right) Quantitative real-time PCR analysis of LSR variants from whole brain, lung, and liver. The expression in liver is much higher than brain or lung, and thus was given its own y axis (right). Splice variant composition is similar between brain and liver (α’ variant followed by α and β variants) but different in the lung (β variant followed by α’ and α variants). Data represent means ± SD (error bars) from three indipendent experiments. (D) Western blot profile of LSR from purified brain capillaries shows a stronger band for the α′ splice variant followed by α and β.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4362448&req=5

fig1: LSR expression in adult mice. (A) Tissue sections of brain, lung, liver, and intestine were colabeled with antibodies directed against LSR (red) and CD31 (green, to label blood vessels). Expression of LSR in CD31+ ECs is only observed in the brain. Bar, 100 µm. (B) Tissue sections from adult mice were labeled with the blood vessel marker BSL I (green), and antibodies against occludin (blue, bicellular TJ) and LSR (red). The merged image indicates that in CNS blood vessels LSR is localized at the tricellular TJ where two bicellular TJ meet. Bar, 5 µm. (C, left) Quantitative real-time PCR analysis of LSR isoforms from purified brain ECs and liver ECs. Analysis indicates no detectable LSR expression in liver ECs but high expression of the α′ variant followed by α and β variants in brain ECs. (C, middle and right) Quantitative real-time PCR analysis of LSR variants from whole brain, lung, and liver. The expression in liver is much higher than brain or lung, and thus was given its own y axis (right). Splice variant composition is similar between brain and liver (α’ variant followed by α and β variants) but different in the lung (β variant followed by α’ and α variants). Data represent means ± SD (error bars) from three indipendent experiments. (D) Western blot profile of LSR from purified brain capillaries shows a stronger band for the α′ splice variant followed by α and β.
Mentions: We first examined LSR expression in different organs by immunostaining tissue sections of brain, liver, lung, and intestine for LSR and double-labeling for ECs with an antibody directed against CD31 (Fig. 1 A). In each of these organs there is robust LSR expression. However, LSR expression only colocalizes with CD31+ ECs in the brain and not in the peripheral organs. In the peripheral tissues, LSR staining is restricted to epithelial cells (lung, intestine) or hepatocytes (liver). These results confirm that Lsr is highly enriched in brain ECs compared with liver, lung, and intestinal ECs.

Bottom Line: One important BBB property is the formation of a paracellular barrier made by tight junctions (TJs) between CNS endothelial cells (ECs).Here, we show that Lipolysis-stimulated lipoprotein receptor (LSR), a component of paracellular junctions at points in which three cell membranes meet, is greatly enriched in CNS ECs compared with ECs in other nonneural tissues.We demonstrate that LSR is specifically expressed at tricellular junctions and that its expression correlates with the onset of BBB formation during embryogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 Department of Pharmacology and Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093 fsohet@ucsd.edu rdaneman@ucsd.edu.

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Related in: MedlinePlus