Proteins of the CNR family are multiple receptors for Reelin.
Layering and positioning of neurons require Reelin- and Src family-associated mammalian Disabled (mDab1). Cadherin-related neuronal receptor (CNR) genes are expressed in neurons of the cortical layer, but not in Cajal-Retzius cells expressing Reelin. This leads us to hypothesize that CNRs bound to Fyn of the Src family are receptors for Reelin. Herein we confirm the association and colocalization of CNR proteins with Reelin. This binding is blocked by CR-50 antibody against Reelin, as well as by monoclonal antibodies produced against CNRs. Both disturb the signaling pathway from Reelin to mDab1 and the positioning of cortical neurons in vitro. These results strongly suggest that the CNR family proteins are multiple Reelin receptors. In addition, differential conservation of the Reelin-binding domain among terrestrial vertebrates may be pertinent to the diversity or complexity of brains.
Senzaki
K
K
Laboratory of Neurobiology and Behavioral Genetics, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan.
Ogawa
M
M
Yagi
T
T
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D019143:Evolution, Molecular; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000091363:Protocadherins; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface; D000091042:Reelin Protein; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012697:Serine Endopeptidases
D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C484820:PCDHA4 protein, human; C485131:PCDHA6 protein, human; C113143:Pcdha4 protein, mouse; C484821:Pcdha4 protein, rat; C113144:Pcdha6 protein, mouse; C485132:Pcdha6 protein, rat; D000091363:Protocadherins; D011956:Receptors, Cell Surface; D000091042:Reelin Protein; C000717129:Reln protein, rat; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases