The L-type amino acid transporter 1 (LAT1) is a protein that acts as a gatekeeper for our cells, moving essential nutrients called amino acids across the cell membrane. This transport function ensures cells receive the building blocks needed to function and thrive. Think of it as a doorman, carefully selecting which molecules can enter and exit.
Mechanism and Transported Molecules
LAT1 (SLC7A5) specializes in transporting large neutral amino acids (LNAAs), including molecules like leucine, phenylalanine, and tryptophan. The transporter does not require sodium and operates as an “antiporter,” exchanging one amino acid from outside the cell for another from inside. This mechanism can be visualized as a revolving door.
To be positioned on the cell’s surface, LAT1 must pair with another protein called 4F2hc (SLC3A2). This partner protein acts as a chaperone, ensuring LAT1 is stable and located in the plasma membrane. While 4F2hc is necessary for localization, LAT1 is the unit responsible for transporting amino acids, a process driven by their concentration gradients.
Physiological Roles and Locations
In a healthy body, LAT1 is found in locations where the demand for amino acids is high. One site is the blood-brain barrier, a shield that regulates which substances enter the brain from the bloodstream. Here, LAT1 ensures a constant supply of amino acids, like tryptophan, for the brain to produce neurotransmitters and function correctly.
The transporter is also highly expressed in the placenta, transporting amino acids from the mother’s circulation to the growing fetus. LAT1 is present in other specialized tissues with high metabolic activity or biological barriers, including the testes, retina, and bone marrow. In activated T-cells of the immune system, LAT1 expression increases to support their rapid proliferation.
Implications in Cancer Development
The role of LAT1 changes in cancer, as many tumor cells display significantly higher levels of LAT1 on their surface compared to healthy cells. This overexpression is an adaptation that fuels the rapid and uncontrolled growth characteristic of tumors. High LAT1 expression has been linked to a poorer prognosis in many types of cancer, including breast, prostate, lung, and colorectal cancers.
By increasing these transporter “gates,” cancer cells can import the large neutral amino acids they need to sustain their high rate of proliferation. Amino acids like leucine are not only used for building new proteins but also act as signaling molecules that activate pathways promoting cell growth, such as the mTOR pathway. This enhanced uptake gives cancer cells a metabolic advantage, allowing them to outcompete normal cells for nutrients.
Therapeutic and Pharmacological Significance
LAT1’s heightened presence in cancer cells has opened new avenues for medical treatment. One strategy involves developing drugs that act as LAT1 inhibitors. These molecules are designed to block the transporter, cutting off the tumor’s supply of amino acids to halt its growth. The inhibitor JPH203, for instance, has shown promise in preclinical studies by suppressing tumor growth.
The transporter’s ability to carry molecules across the blood-brain barrier is also being harnessed for therapeutic benefit. This strategy uses LAT1 as a “Trojan horse” to deliver drugs into the brain that would otherwise be blocked. A well-known example is L-DOPA, a drug used to treat Parkinson’s disease. Because L-DOPA structurally resembles an amino acid, LAT1 transports it into the brain, where it can be converted into the needed neurotransmitter, dopamine. This principle is being explored for delivering chemotherapy to treat brain tumors and other neurological disorders.