biostudies-literatureUnknown240(1)Wang NMegalin is a multiple-ligand receptor that contributes to protein reabsorption in the kidney. Recently, megalin was found to act as a novel endocytic receptor for prorenin. Internalization depended on the (pro)renin receptor. This receptor is an accessory protein of vacuolar H⁺-ATPase (V-ATPase), a complex consisting of 14 subunits and two accessory proteins. Here we explored whether V-ATPase elements other than the (P)RR affect megalin-mediated prorenin uptake. Using RNAi technology, we inhibited each individual V-ATPase subunit in megalin-expressing BN16 cells. Subsequently, we quantified megalin expression and the uptake of prorenin. To unravel the underlying molecular mechanisms, we investigated the adaptor proteins autosomal recessive hypercholesterolemia (ARH) and DisabledJournal of cellular physiologye31518https://www.ebi.ac.uk/biostudies/studies/S-EPMC11694337biostudies-literatureVacuolar H<sup>+</sup>-ATPase and Megalin-Mediated Prorenin Uptake: Focus on Elements Beyond the (Pro)Renin Receptor.PMC11694337Wang NLu XJan Danser AHfalseVacuolar H<sup>+</sup>-ATPase and Megalin-Mediated Prorenin Uptake: Focus on Elements Beyond the (Pro)Renin Receptor.Megalin is a multiple-ligand receptor that contributes to protein reabsorption in the kidney. Recently, megalin was found to act as a novel endocytic receptor for prorenin. Internalization depended on the (pro)renin receptor. This receptor is an accessory protein of vacuolar H⁺-ATPase (V-ATPase), a complex consisting of 14 subunits and two accessory proteins. Here we explored whether V-ATPase elements other than the (P)RR affect megalin-mediated prorenin uptake. Using RNAi technology, we inhibited each individual V-ATPase subunit in megalin-expressing BN16 cells. Subsequently, we quantified megalin expression and the uptake of prorenin. To unravel the underlying molecular mechanisms, we investigated the adaptor proteins autosomal recessive hypercholesterolemia (ARH) and Disabled2025-01-01T00:00:00Z2025 Jan2025-04-04T12:02:52.249Z2025-04-04T12:02:52.249ZS-EPMC116943373974502910.1002/jcp.31518