Reelin is a ligand for lipoprotein receptors.
A signaling pathway involving the extracellular protein Reelin and the intracellular adaptor protein Disabled-1 (Dab1) controls cell positioning during mammalian brain development. Here, we demonstrate that Reelin binds directly to lipoprotein receptors, preferably the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). Binding requires calcium, and it is inhibited in the presence of apoE. Furthermore, the CR-50 monoclonal antibody, which inhibits Reelin function, blocks the association of Reelin with VLDLR. After binding to VLDLR on the cell surface, Reelin is internalized into vesicles. In dissociated neurons, apoE reduces the level of Reelin-induced tyrosine phosphorylation of Dab1. These data suggest that Reelin directs neuronal migration by binding to VLDLR and ApoER2.
D'Arcangelo
G
G
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Homayouni
R
R
Keshvara
L
L
Rice
D S
DS
Sheldon
M
M
Curran
T
T
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002460:Cell Line; D002477:Cells / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D000091042:Reelin Protein; D012697:Serine Endopeptidases
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C036053:VLDL receptor; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D002118:Calcium