Megalin and the neurodevelopmental biology of sonic hedgehog and retinol.
Megalin is a receptor expressed by embryonic epithelia that mediates endocytosis of numerous ligands, including sonic hedgehog (Shh) and retinol, the precursor to retinoic acid (RA). The importance of Shh and RA signaling in neurodevelopment, combined with the fact that megalin-deficient mice show profound neurodevelopmental abnormalities, has raised questions as to the possible role of megalin in Shh and RA signaling. Several mechanisms could explain how megalin influences Shh and RA signaling in the context of neurodevelopment. These include the involvement of megalin in the transport of Shh and retinol within neuroepithelia, as well as direct signal transduction as a response to binding of Shh and retinol to megalin.
McCarthy
Robert A
RA
Medical University of South Carolina, Department of Cell Biology, 171 Ashley Avenue, Charleston, SC 29425-2204, USA.
Argraves
W Scott
WS
D000818:Animals; D004847:Epithelial Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics* / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism*
D053823:Hedgehog Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C509239:SHH protein, human; D015534:Trans-Activators; D014801:Vitamin A