header logo image header logo text
Downloads Login
Research
General Information
ZIRC
ZFIN ID: ZDB-PUB-060501-9
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.
Date: 2006
Source: Journal of Cell Science 119(10): 2127-2137 (Journal)
Registered Authors: Abdelilah-Seyfried, Salim
Keywords: gp330, Cubilin, Disabled 2, Kidney, Endocytosis, PRKCiota, Mpp5
MeSH Terms:
  • Adaptor Proteins, Vesicular Transport/metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Endocytosis
  • Kidney/blood supply
  • Kidney/embryology*
  • Kidney/metabolism*
  • Larva
  • Low Density Lipoprotein Receptor-Related Protein-2/metabolism*
  • Molecular Sequence Data
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
PubMed: 16638803 Full text @ J. Cell Sci.
FIGURES
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.
ADDITIONAL INFORMATION