1. LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation.
- Author
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Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT, and Daneman R
- Subjects
- Animals, Blood-Brain Barrier embryology, Brain blood supply, Cell Line, Encephalomyelitis, Autoimmune, Experimental metabolism, Encephalomyelitis, Autoimmune, Experimental physiopathology, Female, Infarction, Middle Cerebral Artery metabolism, Mice, Inbred C57BL, Mice, Knockout, Blood-Brain Barrier metabolism, Receptors, Lipoprotein physiology, Tight Junctions metabolism
- Abstract
The blood-brain barrier (BBB) is a term used to describe the unique properties of central nervous system (CNS) blood vessels. 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. We further demonstrate that the BBB does not seal during embryogenesis in Lsr knockout mice with a leakage to small molecules. Finally, in mouse models in which BBB was disrupted, including an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and a middle cerebral artery occlusion (MCAO) model of stroke, LSR was down-regulated, linking loss of LSR and pathological BBB leakage., (© 2015 Sohet et al.)
- Published
- 2015
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