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| Item Type: | Article |
|---|---|
| Title: | Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros |
| Creators Name: | Anzenberger, U., Bit-Avragim, N., Rohr, S., Rudolph, F., Dehmel, B., 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 |
| ISSN: | 0021-9533 |
| Publisher: | Company of Biologists |
| Volume: | 119 |
| 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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