PUBLICATION

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

Authors
Anzenberger, U., Bit-Avragim, N., Rohr, S., Rudolph, F., Dehmel, B., Willnow, T.E., and Abdelilah-Seyfried, S.
ID
ZDB-PUB-060501-9
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.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes