Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody.
The neurological mouse mutant strain reeler displays abnormal laminar organization of several brain structures as a consequence of a defect in cell migration during neurodevelopment. This phenotype is a result of the disruption of reelin, a gene encoding a protein that has several structural characteristics of extracellular matrix proteins. To understand the molecular basis of the action of Reelin on neuronal migration, we constructed a full-length reelin clone and used it to direct Reelin expression. Here, we demonstrate that Reelin is a secreted glycoprotein and that a highly charged C-terminal region is essential for secretion. In addition, we demonstrate that an amino acid sequence present in the N-terminal region of Reelin contains an epitope that is recognized by the CR-50 monoclonal antibody. CR-50 was raised against an antigen expressed in normal mouse brain that is absent in reeler mice. The interaction of CR-50 with its epitope leads to the disruption of neural cell aggregation in vitro. Here, we used CR-50 to precipitate Reelin from reticulocyte extracts programmed with reelin mRNA, from cells transfected with reelin clones, and from cerebellar explants. The reelin gene product seems to function as an instructive signal in the regulation of neuronal migration.
D'Arcangelo
G
G
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nakajima
K
K
Miyata
T
T
Ogawa
M
M
Mikoshiba
K
K
Curran
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D019556:COS Cells / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D003001:Cloning, Molecular; D000939:Epitopes; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments / Q000276:immunology; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D014162:Transfection
D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases