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Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros

Item Type:Article
Title:Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros
Creators Name:Anzenberger, U. and Bit-Avragim, N. and Rohr, S. and Rudolph, F. and Dehmel, B. and Willnow, T.E. and Abdelilah-Seyfried, S.
Abstract:Megalin/LRP2 is an endocytic receptor in the proximal tubules of the mammalian kidney that plays a central role in the clearance of metabolites from the glomerular filtrate. To establish a genetic model system for elucidation of molecular components of this retrieval pathway, we characterized orthologous transport processes in the zebrafish. We show that expression of megalin/LRP2 and its co-receptor cubilin is conserved in the larval zebrafish pronephros and demarcates a segment of the pronephric duct that is active in clearance of tracer from the ultrafiltrate. Knock-down of megalin/LRP2 causes lack of Rab4-positive endosomes in the proximal pronephric duct epithelium and abrogates apical endocytosis. Similarly, knock-down of the megalin/LRP2 adaptor Disabled 2 also blocks renal clearance processes. These results demonstrate the conservation of the megalin/LRP2 retrieval pathway between the larval zebrafish pronephros and the mammalian kidney and set the stage for dissection of the renal endocytic machinery in a simple model organism. Using this model system, we provide first genetic evidence that renal tubular endocytosis and formation of endosomes is a ligand-induced process that crucially depends on megalin/LRP2 activity.
Keywords:gp330, Cubilin, Disabled 2, Kidney, Endocytosis, PRKCiota, Mpp5, Animals, Zebrafish
Source:Journal of Cell Science
Publisher:Company of Biologists
Number:Pt. 10
Page Range:2127-2137
Date:15 May 2006
Official Publication:https://doi.org/10.1242/jcs.02954
PubMed:View item in PubMed

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