Abelson interacting protein 1 (Abi-1) is essential for dendrite morphogenesis and synapse formation.
Synaptogenesis and synaptic plasticity depend crucially on the dynamic and locally specific regulation of the actin cytoskeleton. We identified an important component for controlled actin assembly, abelson interacting protein-1 (Abi-1), as a binding partner for the postsynaptic density (PSD) protein ProSAP2/Shank3. During early neuronal development, Abi-1 is localized in neurites and growth cones; at later stages, the protein is enriched in dendritic spines and PSDs, as are components of a trimeric complex consisting of Abi-1, Eps8 and Sos-1. Abi-1 translocates upon NMDA application from PSDs to nuclei. Nuclear entry depends on abelson kinase activity. Abi-1 co-immunoprecipitates with the transcription factor complex of Myc/Max proteins and enhances E-box-regulated gene transcription. Downregulation of Abi-1 by small interfering RNA results in excessive dendrite branching, immature spine and synapse morphology and a reduction of synapses, whereas overexpression of Abi-1 has the opposite effect. Data show that Abi-1 can act as a specific synapto-nuclear messenger and is essentially involved in dendrite and synapse formation.
Proepper
Christian
C
Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
Johannsen
Svenja
S
Liebau
Stefan
S
Dahl
Janine
J
Vaida
Bianca
B
Bockmann
Juergen
J
Kreutz
Michael R
MR
Gundelfinger
Eckart D
ED
Boeckers
Tobias M
TM
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C120532:Shank3 protein, rat; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D016202:N-Methylaspartate; D011392:Proline