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

The L-type amino acid transporter 1 (LAT1) – 4F2hc heterodimer is a membrane-bound transport complex composed of the light chain SLC7A5 and the heavy chain SLC3A2 (Kanai, 2022) [1.1.1]. It functions as a sodium-independent antiporter that mediates the uptake of large neutral amino acids, such as leucine, isoleucine, and phenylalanine, in exchange for intracellular substrates like glutamine (Yan et al., 2021) [1.4.1]. This transport activity is critical for activating the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates cell growth, protein synthesis, and proliferation (Kahlhofer et al., 2023) [1.3.1]. LAT1 is highly overexpressed in a wide variety of human malignancies, including lung, breast, and prostate cancers, where it supports the high metabolic demands of rapidly dividing cells (Sakamoto, 2022) [1.3.3]. Additionally, the complex is a key component of the blood-brain barrier, facilitating the entry of essential nutrients and various pharmaceutical agents, such as L-DOPA and gabapentin, into the central nervous system (Singh & Ecker, 2018) [1.4.4]. Due to its restricted expression in normal tissues and its vital role in tumor progression, the LAT1/4F2hc heterodimer is a significant target for both cancer therapeutics, such as the selective inhibitor nanvuranlat, and targeted drug delivery strategies (Kanai, 2022) [1.1.1].

Other names

SLC7A5/SLC3A2 complexCD98CD98hc/LAT1System L1 transporter4F2 antigenMDU1

Competitive inhibition of large neutral amino acid transport, leading to the depletion of intracellular essential amino acids and subsequent suppression of the mTORC1 signaling pathway, which inhibits protein synthesis and cell proliferation (Kanai, 2022) [1.1.1]. It also acts as a gateway for the delivery of amino acid-mimicking drugs and prodrugs across the blood-brain barrier and into tumor cells (Singh & Ecker, 2018) [1.4.4].