The role of megalin (LRP-2/Gp330) during development
Carolyn E Fisher1, Sarah E M Howie
1Centre for Inflammation Research, Queen's Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH 16 4JT, Scotland, UK. carolyn.fisher@ed.ac.uk
Abstract:
Megalin (LRP-2/GP330), a member of the LDL receptor family, is an endocytic receptor expressed mainly in polarised epithelial cells. Identified as the pathogenic autoantigen of Heymann nephritis in rats, its functions have been studied in greatest detail in adult mammalian kidney, but there is increasing recognition of its involvement in embryonic development. The megalin homologue LRP-1 is essential for growth and development in Caenorhabditis elegans and megalin plays a role in CNS development in zebrafish. There is now also evidence for a homologue in Drosophila. However, most research concerns mammalian embryogenesis; it is widely accepted to be important during forebrain development and the developing renal proximal tubule. Megalin is also expressed in lung, eye, intestine, uterus, oviduct, and male reproductive tract. It is found in yolk sacs and the outer cells of pre-implantation mouse embryos, where interactions with cubilin result in nutrient endocytosis, and it may be important during implantation. Models for megalin interaction(s) with Sonic Hedgehog (Shh) have been proposed. The importance of Shh signalling during embryogenesis is well established; how and when megalin interacts with Shh is becoming a pertinent question in developmental biology.
Insights
Megalin, an endocytic receptor, is crucial for embryonic development, particularly in the brain and kidney. Its interaction with Sonic Hedgehog signaling is a key area of ongoing research in developmental biology.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Megalin (LRP-2/GP330) is an LDL receptor family member and endocytic receptor.
- Primarily studied in adult mammalian kidney, its role in embryonic development is increasingly recognized.
- Homologues exist in C. elegans and Drosophila, highlighting conserved functions.
Purpose of the Study:
- To review the established and emerging roles of megalin in mammalian embryogenesis.
- To highlight the importance of megalin in forebrain and renal proximal tubule development.
- To explore the proposed interactions between megalin and Sonic Hedgehog (Shh) signaling.
Main Methods:
- Literature review of studies on megalin function in development.
- Analysis of megalin expression patterns in embryonic tissues.
- Examination of proposed models for megalin-Shh interactions.
Main Results:
- Megalin is essential for forebrain development and the developing renal proximal tubule in mammals.
- It plays a role in nutrient endocytosis in pre-implantation mouse embryos via cubilin interaction.
- Megalin is expressed in various embryonic tissues including yolk sacs and reproductive tracts.
Conclusions:
- Megalin is a significant factor in mammalian embryonic development, with critical roles in neural and renal systems.
- Understanding megalin's interaction with Sonic Hedgehog signaling is a pertinent question for developmental biology.
- Further research is needed to elucidate the precise mechanisms and timing of megalin-Shh crosstalk.
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