L-type amino acid transporter 1 – 4F2 cell-surface antigen heavy chain complex (LAT1–4F2hc)

The L-type amino acid transporter 1 (LAT1) – 4F2 cell-surface antigen heavy chain (4F2hc) complex is a heterodimeric membrane protein consisting of the catalytic light chain LAT1 (SLC7A5) and the chaperone heavy chain 4F2hc (SLC3A2), covalently linked by a disulfide bond [1, 2]. This complex functions as a sodium-independent antiporter that mediates the high-affinity uptake of large neutral essential amino acids, such as leucine, phenylalanine, and tryptophan, in exchange for intracellular substrates like glutamine [2, 5]. LAT1 is significantly overexpressed in a wide range of human cancers to support the increased metabolic and proliferative demands of tumor cells, primarily by activating the mTORC1 signaling pathway [1, 8]. Beyond its role in oncology, the complex is a critical component of the blood-brain barrier and placental barrier, facilitating the transport of nutrients and various drugs, including L-DOPA and gabapentin [9, 15]. Therapeutic strategies targeting this complex include the development of small-molecule inhibitors like JPH203 to starve cancer cells, as well as utilizing the transporter as a vehicle for targeted drug delivery into the central nervous system [6, 16].

Other names

SLC7A5/SLC3A2 complexCD98/LAT1 complexSystem L amino acid transporter 1CD98hc/LAT1Heteromeric amino acid transporter 1SLC7A5-SLC3A2 heterodimer

Competitive inhibition of large neutral amino acid transport, leading to intracellular amino acid depletion and subsequent downregulation of the mTORC1 signaling pathway; additionally, the complex facilitates the transport of amino acid-mimetic drugs and prodrugs across biological barriers such as the blood-brain barrier.