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 II and Dcx interact in vivo. Several Dcx constructs that mimic human DCX mutant alleles failed to interact with neurabin II. Since Dcx and neurabin II colocalized in the developing and adult brain, a neurabin II-DCX heterodimer may be involved in neuronal migration and dendritic spine formation.
Tsukada
Miki
M
Max Planck Institute for Experimental Endocrinology, Feodor-Lynen-Strasse 7, Hannover 30625, Germany.
Prokscha
Alexander
A
Oldekamp
Judit
J
Eichele
Gregor
G
D000483:Alleles; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002465:Cell Movement; D003712:Dendrites / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020080:Tandem Repeat Sequences; D013687:Telencephalon / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000099273:Neurabins
D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011994:Recombinant Proteins; D000099273:Neurabins; C000714328:DCX protein, human; C000714847:Dcx protein, mouse