Large neutral amino acids transporter small subunit 1-4F2 cell-surface antigen heavy chain complex (LAT1-4F2hc) (LAT1-4F2hc)

The Large neutral amino acids transporter small subunit 1-4F2 cell-surface antigen heavy chain complex (LAT1-4F2hc) is a transmembrane protein complex that functions as a sodium-independent, high-affinity exchanger of large neutral amino acids. The complex consists of the light chain LAT1 (SLC7A5), which provides the transport activity, and the heavy chain 4F2hc (SLC3A2), which is essential for the stability and membrane localization of the transporter (UniProt: P48023, P08195). It primarily transports essential amino acids such as leucine, isoleucine, and phenylalanine into the cell in exchange for intracellular substrates like glutamine, thereby playing a critical role in nutrient sensing and the activation of the mTORC1 signaling pathway (Napolitano et al., 2015; PubMed: 25911098). While LAT1-4F2hc expression is relatively low in most healthy adult tissues, it is highly upregulated in various malignancies, including lung, colon, and breast cancers, to support the increased metabolic demands of rapidly proliferating cells (Okano et al., 2020; PubMed: 32154390). This differential expression makes it an attractive therapeutic target and a diagnostic biomarker. Pharmacological inhibition of the complex, notably by the selective inhibitor JPH203, has demonstrated the ability to induce amino acid starvation and inhibit tumor growth in clinical trials (Oda et al., 2010; PubMed: 20406990). Furthermore, the transporter is exploited for the delivery of amino acid-based drugs and imaging tracers, such as [18F]-fluoroethyl-L-tyrosine, used in oncology (PubMed: 23832071).

Other names

SLC7A5-SLC3A2 complexCD98LAT1-CD98hcLarge neutral amino acids transporter 14F2hc-LAT1MDU14F2CD98HC

Competitive inhibition of the transport of essential amino acids (e.g., leucine), which leads to intracellular amino acid depletion, suppression of the mTORC1 signaling pathway, and subsequent inhibition of protein synthesis and cell proliferation (PubMed: 20406990, 25911098).