Crossing the Borders: the amino acid transporter LAT1 (SLC7A5) in the Blood-Brain Barrier

Abstract

The blood-brain barrier is an anatomical structure responsible for controlling the flux of nutrients, metabolites, and xenobiotics into and out of the brain. This fundamental function is carried out through the coordinated action of specific ion channels and membrane transporters belonging to the SLC and ABC superfamilies. Indeed, membrane transporter expression in the BBB is less redundant than in other parts of the body. Therefore, any alteration to one of these proteins may pose a threat to the brain. The fifth member of the SLC7 family, which is expressed at the BBB has been the subject of much research over the years. SLC7A5, also known as LAT1, is a plasma membrane transporter of essential amino acids, whose role in brain development is well recognised. The protein is expressed in the membranes of BBB vessels, neurons, and microglia, creating a connection between different areas of the human brain. LAT1 received significant attention in the context of brain tumor treatment, particularly for glioblastoma multiforme, a malignancy with a poor prognosis characterised by fatal relapses. Since several drugs are also substrates of LAT1, its expression at the BBB could be exploited to deliver drugs that target brain diseases. This review describes the functional, structural, and regulatory features of LAT1, focusing on pharmacology in the context of brain homeostasis.