Identification of neurabin II as a novel doublecortin interacting protein

The neuronal migration protein doublecortin (DCX) that associates with microtubules through a tandem DCX repeat, is required for the development of the complex architecture of the human cerebral cortex. Using a yeast two-hybrid screen with Dcx as bait, we have isolated neurabin II/spinophilin, an F-actin binding protein known to play a role in dendritic spine formation. The coiled-coil domain of neurabin II binds to a DCX region encompassing the C-terminal portion of the second DCX repeat and the N-terminal portion of the Ser/Pro-rich domain. Immunoprecipitation experiments with brain extracts show that neurabin H and Dcx interact in vivo. Several Dcx constructs that mimic human DCX mutant alleles failed to interact with neurabin II. Since Dcx and neurabin H colocalized in the developing and adult brain, a neurabin II-DCX heterodimer may be involved in neuronal migration and dendritic spine formation. (C) 2003 Elsevier Ireland Ltd. All rights reserved.