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Megalin with neurodevelopment

Megalin is a member of the LDL receptor family that mediates endocytosis of a variety of molecules by endothelial cells. In adults, it is particularly important for uptake of vitamins and their carriers by the kidney. Less is known about its function during development, but the perinatal death of megalin-knockout mice indicates that its role is essential. In a Commentary on p. 955, Robert McCarthy and Scott Argraves discuss recent studies that reveal that megalin modulates signalling by two key morphogens – sonic hedgehog (SHH) and retinoic acid (RA) – during development of the nervous system. Megalin is known to be expressed on the apical surfaces of neuroepithelia, and the knockouts display numerous neurodevelopmental defects. The new work suggests that megalin binds to and endocytoses retinol (the precursor of RA) and probably transports it to adjacent cells that synthesize RA. It has also shown that megalin binds to SHH, which like RA is critical for neurodevelopment. The consequences of this are less clear. Megalin might simply act as a signalling receptor for SHH, but it is more likely to regulate trafficking of SHH and/or its receptors Patched (Ptc) and Smoothened (Smo).

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Megalin and the neurodevelopmental biology of sonic hedgehog and retinol

Robert A. McCarthy and W. Scott Argraves
JCS 2003 116: 955-960. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?