Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.
By O. Yanagida, Yoshikatsu Kanai, A. Chairoungdua, Do Kyung Kim, H. Segawa, T. Nii, S. Cha, H. Matsuo, Jun-ichi Fukushima, Yoshiki Fukasawa and 10 more. Biochimica et Biophysica Acta, 2001
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System L is a major nutrient transport system responsible for the transport of large neutral amino acids including several essential amino acids. We previously identified a transporter (L-type amino acid transporter 1: LAT1) subserving system L in C6 rat glioma cells and demonstrated that LAT1 requires 4F2 heavy chain (4F2hc) for its functional expression. Since its oncofetal expression was suggested in the rat liver, it has been proposed that LAT1 plays a critical role in cell growth and proliferation. In the present study, we have examined the function of human LAT1 (hLAT1) and its expression in human tissues and tumor cell lines. When expressed in Xenopus oocytes with human 4F2hc (h4F2hc), hLAT1 transports large neutral amino acids with high affinity (K(m)= approximately 15- approximately 50 microM) and L-glutamine and L-asparagine with low affinity (K(m)= approximately 1.5- approximately 2 mM). hLAT1 also transports D-amino acids such as D-leucine and D-phenylalanine. In addition, we show that hLAT1 accepts an amino acid-related anti-cancer agent melphalan. When loaded intracellularly, L-leucine and L-glutamine but not L-alanine are effluxed by extracellular substrates, confirming that hLAT1 mediates an amino acid exchange. hLAT1 mRNA is highly expressed in the human fetal liver, bone marrow, placenta, testis and brain. We have found that, while all the tumor cell lines examined express hLAT1 messages, the expression of h4F2hc is varied particularly in leukemia cell lines. In Western blot analysis, hLAT1 and h4F2hc have been confirmed to be linked to each other via a disulfide bond in T24 human bladder carcinoma cells. Finally, in in vitro translation, we show that hLAT1 is not a glycosylated protein even though an N-glycosylation site has been predicted in its extracellular loop, consistent with the property of the classical 4F2 light chain. The properties of the hLAT1/h4F2hc complex would support the roles of this transporter in providing cells with essential amino acids for cell growth and cellular responses, and in distributing amino acid-related compounds.
Subfields: Biochemistry, Clinical Biochemistry, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/cf43ae4f0785493d63bd5ed002e72e5f53c9701e
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Citations in the corpus
- Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy (2009, unknown): “Since SLC7A5/SLC3A2 is capable of using L-glutamine as an efflux substrate (Meier et al., 2002; Yanagida et al., 2001), we tested the hypothesis that EAA regulates the efflux of intracellular L-glutamine by quantifying its presence in medium after EAA treatment.”
- CATs and HATs: the SLC7 family of amino acid transporters (2004, result): “This, together with later observations that LAT1 is expressed in most tested tumours and tumour cell lines, suggests that LAT1-4F2hc may play an important role in many growing cells [65, 68].”
- The SLC3 and SLC7 families of amino acid transporters. (2013, background): “Human 4F2hc/LAT1 has a high affinity (Km 50 lM) for large neutral amino acids and a lower affinity (Km 1–2 mM) for glutamine and asparagine exchange (Yanagida et al., 2001).”