The reelin receptor ApoER2 recruits JNK-interacting proteins-1 and-2

Correct positioning of neurons during embryonic development of the brain de pends, among other processes, on the proper transmission of the reelin sign al into the migrating cells via the interplay of its receptors with cytopla smic signal transducers. Cellular components of this signaling pathway char acterized to date are cell surface receptors for reelin like apolipoprotein E receptor 2 (ApoER2), very low density lipoprotein receptor (VLDLR), and cadherin-related neuronal receptors, and intracellular components like Disa bled-1 and the nonreceptor tyrosine kinase Fyn, which bind to the intracell ular domains of the ApoER2 and VLDL receptor or of cadherin-related neurona l receptors, respectively. Here we show that ApoER2, but not VLDLR, also bi nds the family of JNK-interacting proteins (JIPs), which act as molecular s caffolds for the JNK-signaling pathway. The ApoER2 binding domain on JIP-2 does not overlap with the binding sites for MLK3, MKK7, and JNK. These resu lts suggest that ApoER2 is able to assemble a multiprotein complex containi ng Disabled-1 and JIPs, together with their binding partners, to the cell s urface of neurons. This complex might participate in ApoER2-specific reelin signaling and thus would explain the different phenotype of mice lacking t he ApoER2 from that of VLDLR-deficient mice.