Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros
- Anzenberger, U., Bit-Avragim, N., Rohr, S., Rudolph, F., Dehmel, B., Willnow, T.E., and Abdelilah-Seyfried, S.
- Journal of Cell Science 119(10): 2127-2137 (Journal)
- Registered Authors
- Abdelilah-Seyfried, Salim
- gp330, Cubilin, Disabled 2, Kidney, Endocytosis, PRKCiota, Mpp5
- MeSH Terms
- Adaptor Proteins, Vesicular Transport/metabolism
- Amino Acid Sequence
- Animals, Genetically Modified
- Kidney/blood supply
- Low Density Lipoprotein Receptor-Related Protein-2/metabolism*
- Molecular Sequence Data
- 16638803 Full text @ J. Cell Sci.
Anzenberger, U., Bit-Avragim, N., Rohr, S., Rudolph, F., Dehmel, B., Willnow, T.E., and Abdelilah-Seyfried, S. (2006) Elucidation of megalin/LRP2-dependent endocytic transport processes in the larval zebrafish pronephros. Journal of Cell Science. 119(10):2127-2137.
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.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes