More Reelin Receptors

Abstract

Proper development of the mammalian brain involves organization of cortical neurons into distinct layers. Reelin is a secreted glycoprotein that communicates positional information to neurons during this process. Recently, two different cell surface lipid receptors were identified as putative receptors for Reelin. Now, the eight member family of cadherin-related neuronal receptors (CNRs) joins this list. Senzaki et al . report that CNR binds to Reelin when both proteins were expressed in cultured cells. The Reelin binding region was localized to an amino-terminal extracellular cadherin (EC) domain in CNR, a domain found in cadherins that is known to mediate protein-protein interactions. Moreoever, an Arg-Gly-Asp (RGD) motif contained within this EC domain, a consensus sequence that mediates fibronectin-integrin interactions, is required for CNR-Reelin interaction. Antibodies generated to the Reelin-binding domain of CNR disrupted organization of cultured cortical neurons and inhibited Reelin-induced tyrosine phosphorylation of Disabled (mDab1), an intracellular adaptor protein in Reelin target cells. The authors propose that during developmental positioning of cortical neurons, Reelin association with CNR activates Fyn, a tyrosine kinase known to be associated with CNR. Fyn might then phosphorylate mDab1 and possibly other downstream effector molecules. Senasaki, K., Ogawa, M., and Yagi, T. (1999) Proteins of the CNR family are multiple receptors for Reelin. Cell 99 : 635-647. [Online Journal]