Proteins of the CNR family are multiple receptors for reelin

Layering and positioning of neurons require Reelin-and Src family-associate d mammalian Disabled (mDab1). Cadherin-related neuronal receptor (CNR) gene s 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 Fy n of the Src family are receptors for Reelin. Herein we confirm the associa tion and colocalization of CNR proteins with Reelin. This binding is blocke d by CR-50 antibody against Reelin, as well as by monoclonal antibodies pro duced against CNRs. Both disturb the signaling pathway from Reelin to mDab1 and the positioning of cortical neurons in vitro. These results strongly s uggest that the CNR family proteins are multiple Reelin receptors. In addit ion, differential conservation of the Reelin-binding domain among terrestri al vertebrates may be pertinent to the diversity or complexity of brains.