The human LAT1–4F2hc (SLC7A5–SLC3A2) transporter complex: Physiological and pathophysiological implications

Abstract

LAT1 and 4F2hc form a heterodimeric membrane protein complex, which functions as one of the best characterized amino acid transporters. Since LAT1–4F2hc is required for the efficient uptake of essential amino acids and hormones, it promotes cellular growth, in part, by stimulating mTORC1 (mechanistic target of rapamycin complex 1) signalling and by repressing the integrated stress response (ISR). Gain or loss of LAT1–4F2hc function is associated with cancer, diabetes, and immunological and neurological diseases. Hence, LAT1–4F2hc represents an attractive drug target for disease treatment. Specific targeting of LAT1–4F2hc will be facilitated by the increasingly detailed understanding of its molecular architecture, which provides important concepts for its function and regulation. Here, we summarize (i) structural insights that help to explain how LAT1 and 4F2hc assemble to transport amino acids across membranes, (ii) the role of LAT1–4F2hc in key metabolic signalling pathways, and (iii) how derailing these processes could contribute to diseases.

Immunoreactivity against SLC3A2 in high grade gliomas displays positive correlation with glioblastoma patient survival: Potential target for glioma diagnosis and therapy

“…These results indicates that GBM patients with higher SLC3A2 immunoreactivity were more likely to display longer survival time. SLC3A2 is over-expressed by GBM and is a part of an aminoacid channel complex that is essential for the survival of GBM cells [27]. Therefore, we reasoned that SLC3A2 antibodies interfere with the functions of SLC3A2 on the cell membrane and limit the nourishment of GBM cells, thereby restricting the growth of the GBM tumors.…”

“…These results indicates that GBM patients with higher SLC3A2 immunoreactivity were more likely to display longer survival time. SLC3A2 is over-expressed by GBM and is a part of an aminoacid channel complex that is essential for the survival of GBM cells [27]. Therefore, we reasoned that SLC3A2…”

Proximity Interactome Analysis of Super Conserved Receptors Expressed in the Brain Identifies EPB41L2, SLC3A2, and LRBA as Main Partners

“…We also specifically identified the solute carrier family 3 member 2 protein (SLC3A2), belonging to the protein family of the solute carrier (SLC), a large group of membrane transport proteins enriched in SREB1 and SREB3 (Figure 2d, panel 4). SLC3A2 is a transmembrane glycoprotein that serves as the heavy chain subunit of L amino acid transporters [41]. Most selected candidates were not exclusive to a single receptor but identified as proximal interactors for the other SREBs and/or CMKLR1 with a lower fold change or significance.…”

Transmembrane transporter proteins: Capturing transport in motion

“…The focused review by Kahlhofer and Teis 15 delves into the physiology and pathophysiology of the LAT1‐4F2hc heterodimeric complex. LATs, also known as non‐glycosylated light chain transporters, interact with glycosylated heavy chain transporters from the SLC3 family (4F2hc/SLC3A2 or rBAT/SLC3A1) to form heteromeric amino acid transporters (HAT).…”