Figure 5.

Localization and function of amino acid exchangers (with emphasize on branched-chain amino acids, BCAAs) ) in cell membranes of the neurovascular unit.

Endothelial cells (ECs) line the blood vessels lumen. They are connected via transmembrane tight junction proteins, which provide tight adhesion and facilitate communication between ECs. The endothelium is separated from other cells by basal lamina. Astrocyte end-feet ensheath the vessel walls. The L1 system transporters possess a critical role in maintaining physiological levels of BCAAs and present in luminal and abluminal membrane of endothelial cells. Additionally, these glutamine (Gln) exchangers are highly expressed in astrocytes and neurons. Alanine (Ala), Serine (Ser), Cysteine (Cys) Transporter 2 (ASCT2) and SNAT transporters are responsible for glutamine influx and present in neurons. Glutamate (Glu) is released from neurons to the synaptic cleft during excitatory neurotransmission. The excitatory amino acid transporters (EAAT) is expressed in astrocytes and responsible for glutamate removal from the synaptic cleft. Glutamate undergoes amidation by glutamine synthetase (GS) in astrocytes to form glutamine, which is released to extracellular space and uptaken by neurons.