L-type amino acid transporter 1 in complex with 4F2hc (LAT1-4F2hc)

The L-type amino acid transporter 1 (LAT1) in complex with 4F2hc (SLC3A2) is a heterodimeric membrane protein that functions as a sodium-independent, pH-independent antiporter of large neutral amino acids, such as leucine, phenylalanine, and tryptophan [1, 4, 12]. The complex consists of the functional light chain LAT1 (SLC7A5) and the heavy chain chaperone 4F2hc (SLC3A2), which are covalently linked by a disulfide bond to ensure proper plasma membrane localization and stability [4, 13, 14]. This transporter is crucial for providing essential amino acids to cells, thereby activating the mTORC1 signaling pathway and promoting cell growth, proliferation, and protein synthesis [1, 2, 13]. While its expression is limited in most normal tissues, it is highly upregulated in the blood-brain barrier, placenta, and a wide variety of human cancers, where it supports the high metabolic demands of rapidly dividing cells [4, 8, 15]. Consequently, the LAT1-4F2hc complex is a significant therapeutic target for cancer treatment, with specific inhibitors like JPH203 showing promise in suppressing tumor growth by inducing amino acid starvation [5, 8, 13]. Additionally, its high expression at the blood-brain barrier is exploited for the targeted delivery of amino acid-mimicking drugs, such as L-DOPA and gabapentin, into the central nervous system [4, 10, 12].

Other names

SLC7A5-SLC3A2 complexCD98CD98hcLAT1-CD98hcLarge neutral amino acids transporter 1System L amino acid transporter 1

Competitive inhibition of large neutral amino acid transport; Downregulation of the mTORC1 signaling pathway; Facilitation of transmembrane drug delivery via substrate mimicry