Impact of claudin-4 in the expression of transporters of amino acids and the uptake of essential amino acids in HGSOC cells. The effect of claudin-4 manipulation (overexpression and downregulation) in the expression of SLC1A5 and LAT1 was measured via immunoblotting in HGSOC cells (OVCAR8, OVCA429, and OVCAR3). Direct amino acid uptake (essential amino acids, EAA; [3H]leucine) was analyzed in OVCAR3 cells (culture for 24 hours). A and B, Top, show representative immunoblots for SLC1A5 and LAT1 in HGSOC cells during claudin-4 disruption, respectively; (bottom), corresponding quantification (four independent experiments). C, Left, illustration highlighting a heterodimer formed by LAT and SLC3A2 which internalizes essential amino acids; right, uptake measurement of the essential amino acid leucine ([3H]leucine; three independent experiments; Two-tail t test). D, Model [adapted from reference: (54)] proposing an axis formed by claudin-4, SLC1A5, and LAT1 which could regulate autophagy in HGSOC cells. In this model, claudin-4 is contributing to determine the intracellular localization of theses transporters of amino acids, and possibly stabilizing their function in membranes. (significance, P < 0.05). Graphs show mean and SEM.
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Villagómez et al. (2024) studied this question.
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