The Role of BAR Proteins and the Glycocalyx in Brain Endothelium Transcytosis

Abstract

Within the brain, endothelial cells lining the blood vessels meticulously coordinate the transport of nutrients, energy metabolites and other macromolecules essential in maintaining an appropriate activity of the brain. While small molecules are pumped across specialised molecular transporters, large macromolecular cargos are shuttled from one side to the other through membrane-bound carriers formed by endocytosis on one side, trafficked to the other side and released by exocytosis. Such a process is collectively known as transcytosis. The brain endothelium is recognised to possess an intricate vesicular endosomal network that mediates the transcellular transport of cargos from blood-to-brain and brain-to-blood. However, mounting evidence suggests that brain endothelial cells (BECs) employ a more direct route via tubular carriers for a fast and efficient transport from the blood to the brain. Here, we compile the mechanism of transcytosis in BECs, in which we highlight intracellular trafficking mediated by tubulation, and emphasise the possible role in transcytosis of the Bin/Amphiphysin/Rvs (BAR) proteins and glycocalyx (GC)—a layer of sugars covering BECs, in transcytosis. Both BAR proteins and the GC are intrinsically associated with cell membranes and involved in the modulation and shaping of these membranes. Hence, we aim to summarise the machinery involved in transcytosis in BECs and highlight an uncovered role of BAR proteins and the GC at the brain endothelium.

A Multiscale Study of Phosphorylcholine Driven Cellular Phenotypic Targeting

“…Lectin has a high binding affinity for glycoprotein N-acetylglucosamines and has been used to identify the glycocalyx composition. 40 We show that the HDF cell line saturates at lower lectin concentrations than FaDu and THP-1, indicating the presence of more sugars in the glycocalyx. In Figure 5b we use the experimental values from Figure 1a to fix the N CD81 , N CD36 , and N SRB1 for the three different cell lines, to estimate the effect of the Psome radius and the degree of polymerization N PC on the binding energy.…”

“…We characterize the differences in cell glycocalyx through lectin-binding assay (Figure a). Lectin has a high binding affinity for glycoprotein N-acetylglucosamines and has been used to identify the glycocalyx composition . We show that the HDF cell line saturates at lower lectin concentrations than FaDu and THP-1, indicating the presence of more sugars in the glycocalyx.…”

Identification of lamprey variable lymphocyte receptors that target the brain vasculature

“…Accordingly, heterogeneity in adhesion molecule glycosylation has been suggested as a vascular and disease-specific molecular zip code for inflammatory responses 59 . It has also been suggested that the glycocalyx may play an important role in transcytosis at the BBB 60 . Despite the established importance of the BBB glycocalyx, the discovery and development of BBB-targeting reagents recognizing BBB glyco-epitopes has been under-pursued, perhaps because of the suboptimal glyco-recognition of Ig-based binding scaffolds that have been used in BBB screens 18 , 61 .…”

The Ism between Endothelial Cilia and Endothelial Nanotubules Is an Evolving Concept in the Genesis of the BBB

“…The role of f-actin in “membrane shaping” is key to cellular processes such as transcytosis, cell division, filopodial protrusions and NT formation [ 31 , 34 , 36 ]. The formation of membranous structures is endorsed by the role of regulators of membrane curvature, which is a family of proteins that comprises the crescent-shaped Bin/Amphiphysin/Rvs (BAR) domain [ 68 ].…”