Functions of lipid raft membrane microdomains at the blood–brain barrier

Abstract

The blood-brain barrier (BBB) is a highly specialized structural and functional component of the central nervous system that separates the circulating blood from the brain and spinal cord parenchyma. Brain endothelial cells (BECs) that primarily constitute the BBB are tightly interconnected by multiprotein complexes, the adherens junctions and the tight junctions, thereby creating a highly restrictive cellular barrier. Lipid-enriched membrane microdomain compartmentalization is an inherent property of BECs and allows for the apicobasal polarity of brain endothelium, temporal and spatial coordination of cell signaling events, and actin remodeling. In this manuscript, we review the role of membrane microdomains, in particular lipid rafts, in the BBB under physiological conditions and during leukocyte transmigration/diapedesis. Furthermore, we propose a classification of endothelial membrane microdomains based on their function, or at least on the function ascribed to the molecules included in such heterogeneous rafts: (1) rafts associated with interendothelial junctions and adhesion of BECs to basal lamina (scaffolding rafts); (2) rafts involved in immune cell adhesion and migration across brain endothelium (adhesion rafts); (3) rafts associated with transendothelial transport of nutrients and ions (transporter rafts).

Substrate-Immobilized HIV-1 Tat Drives VEGFR2/α v β 3 –Integrin Complex Formation and Polarization in Endothelial Cells

“…28 We demonstrate that ECs undergo polarization after their adhesion to substrate-immobilized Tat with the specific recruitment of VEGFR2 and a v  3 at the basal aspect of adherent cells. HIV-1 Tat shares several biological features with classical cell adhesive proteins and AGFs, being able to accumulate in the ECM, 9 to bind integrins and TKRs 29 and to modulate EC adhesion, migration, proliferation, 17 and cytoskeleton organization.…”

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

“…While cell membrane lipid raft domains are integral parts of the TJ spatial assemblies (Dodelet-Devillers et al, 2009; Li et al, 2009; Eum et al, 2014), lipid raft domains also form signaling platforms to trigger redox-signaling cascades. Specifically, membrane lipid rafts in endothelial cells serve as a platform to recruit and activate NADPH oxidase systems, causing cellular oxidative stress (Patel and Insel, 2009).…”

“…The blood–brain barrier (BBB) is a highly specialized structural and functional barrier separating the microenvironment of the central nervous system (CNS) from the peripheral circulation by restricting paracellular movement of ions and solutes across the brain endothelium (Dodelet-Devillers et al, 2009). Disruption of the BBB is a common event in the development of several CNS disorders including stroke, septic encephalopathy, brain tumors, and ischemia/reperfusion injury (Forster, 2008; Banks, 2015; Shetty et al, 2014).…”

Anatomy and Physiology of the Blood–Brain Barriers

“…In brain endothelium, such rafts (Cayrol et al 2011 ) have documented functions in leukocyte adhesion and traffi cking, junctional molecular architecture and localisation and function of transporters (Dodelet-Devillers et al 2009 ). A subset of rafts form caveolae, with high expression of caveolin-1, and can be further classifi ed by function in scaffolding for junctional proteins and adhesion to basal lamina, immune cell adhesion and recruitment and transendothelial transport .…”