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.
Highlights
Blood vessels in the brain are organised with a surprising precision, supporting the major neural circuits responsible for sensation, cognition, memory and motion [1]
brain endothelial cells (BECs) differentiate between transcytosis or degradation, as well as how the full molecular machinery is implicated in transcytosis
BECs? What molecular machinery is involved in the shuttling of a cargo across BECs?
Summary
Blood vessels in the brain are organised with a surprising precision, supporting the major neural circuits responsible for sensation, cognition, memory and motion [1]. Recent findings suggest that BECs employ sorting tubules as a fast mechanism of transcytosis, in which the cargo is efficiently transported across via tubular carriers, avoiding endosomes and lysosomal degradation [6,7] These results corroborate evidence from the 1970s and 1990s, in which it was suggested that intracellular trafficking occurs through a network of tubules at the brain endothelium [8,9,10,11,12]. Even though the BAR proteins and GC are abundant in the brain endothelium [7,18,19,20] and intrinsically associated with the cell membrane and membrane curvature, these elements are often neglected in terms of their role in the formation of vesicular or tubular carriers for the transport and intracellular fate of the cargo in endothelial cells. We review two elements that remain unexplored in transcytosis at the brain endothelium—BAR proteins and the GC—and attempt to raise the relevance of both in the mechanisms governing vesicular and tubular trafficking in transendothelial transcytosis
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