LAT1

L-Type Amino Acid Transporter 1 (LAT1) is a sodium- and pH-independent transporter responsible for the uptake of large neutral amino acids and several clinically used drugs, including L-DOPA, gabapentin, baclofen, and melphalan. LAT1 functions as a heterodimer consisting of a light chain (SLC7A5) and a heavy chain (CD98/4F2hc; SLC3A2), which is required for proper localization and activity of the transporter.

LAT1 is highly expressed in tissues with high amino acid demand, such as the brain and placenta, and is frequently upregulated in cancer cells and activated immune cells. Its expression at the blood–brain barrier and in several disease-relevant tissues makes LAT1 an attractive target for transporter-mediated drug delivery and therapeutic intervention.

LAT1 is one of the primary transporter platforms in our research. We investigate LAT1 as both a carrier and a therapeutic target, with applications ranging from brain- and cell-selective drug delivery to cancer-, pancreatic-, placental-, and mitochondrial-targeted therapies.

Selected Publications

Bahrami, K.; Järvinen, J.; Laitinen, T.; Reinisalo, M.; Honkakoski, P.; Poso, A.; Huttunen, K. M.; Rautio, J. Structural features affecting selectivity of LAT1-targeted phenylalanine drug conjugates. Molecular Pharmaceutics, 2022, 20(1):206-218. https://doi.org/10.1021/acs.molpharmaceut.2c00594

Huttunen, J.; Agami, M.; Tampio, J.; Montaser, A. B.; Huttunen, K. M. Comparison of Experimental Strategies to Study L-Type Amino Acid Transporter 1 (LAT1) Utilization by Ligands. Molecules, 2021, 27(1), 37, 37-57. https://doi.org/10.3390/molecules27010037

Jalkanen, A.; Ihalainen, J.; Lehtonen, M.; Forsberg, M. M.; Rautio, J.; Huttunen, K. M.; Gynther, M. Species differences between mice and rats in the pharmacology of a LAT1-utilizing compound. International Journal of Pharmaceutics, 2021, 596: 120300. https://doi.org/10.1016/j.ijpharm.2021.120300

Kärkkäinen, J.; Laitinen, T.; Markowicz-Piasecka, M.; Montaser, A.; Lehtonen, M.; Rautio, J.; Gynther, M.; Poso, A.; Huttunen, K.M. Molecular characteristics supporting l-Type amino acid transporter 1 (LAT1)-mediated translocation. Bioorganic Chemistry, 2021, 112: 104921. https://doi.org/10.1016/j.bioorg.2021.104921

Huttunen J.; Gynther, M.; Vellonen, K.-S.; Huttunen, K. M. L-Type Amino Acid Transporter 1 (LAT1)-Utilizing Prodrugs Are Carrier-Selective Despite Having Low Affinity for Organic Anion Transporting Polypeptides (OATPs). International Journal of Pharmaceutics, 2019, 571, 11871410. http://doi.org/10.1016/j.ijpharm.2019.118714

Kärkkäinen, J.; Gynther, M.; Kokkola, T.; Petsalo, A.; Auriola, S.; Lahtela-Kakkonen, M.; Laine, K.; Rautio, J.; Huttunen, K. M. Structural Properties for Selective and Efficient L-Type Amino Acid Transporter 1 (LAT1)- Mediated Cellular Uptake. International Journal of Pharmaceutics, 2018, 544 (1), 91-99. http://doi.org/10.1016/j.ijpharm.2018.04.025

Huttunen, K. M.; Huttunen, J.; Aufderhaar, I.; Gynther, M.; Denny, W. A.; Spicer, J. A. L-Type Amino Acid Transporter 1 (LAT1)- Mediated Targeted Delivery of Perforin Inhibitors. International Journal of Pharmaceutics, 2015, 498 (1-2), 205-216. http://dx.doi.org/10.1016/j.ijpharm.2015.12.034

Ylikangas, H.; Malmioja, K.; Peura, L.; Gynther, M.; Nwachukwu, E. O.; Leppänen, J.; Laine, K.; Rautio, J.; Lahtela-Kakkonen, M.; Huttunen, K. M.; Poso, A. Quantitative Insights for the Design of Compounds Recognized by L-Type Amino Acid Transporter 1 (LAT1). ChemMedChem, 2014, 9 (12), 2699-2707. http://dx.doi.org/10.1002/cmdc.201402281