Journal of Cell Science 116, e602-e602 (2003)
Copyright © 2003 The Company of Biologists Limited
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).
Related articles in JCS:
- 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]
