title: Heterogeneous nuclear ribonucleoprotein k interacts with Abi-1 at postsynaptic sites and modulates dendritic spine morphology.
abstract: BACKGROUND
  Abelson-interacting protein 1 (Abi-1) plays an important role for dendritic branching and synapse formation in the central nervous system. It is localized at the postsynaptic density (PSD) and rapidly translocates to the nucleus upon synaptic stimulation. At PSDs Abi-1 is in a complex with several other proteins including WASP/WAVE or cortactin thereby regulating the actin cytoskeleton via the Arp 2/3 complex.
  
  
  RESULTS
  We identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a 65 kDa ssDNA/RNA-binding-protein that is involved in multiple intracellular signaling cascades, as a binding partner of Abi-1 at postsynaptic sites. The interaction with the Abi-1 SH3 domain is mediated by the hnRNPK-interaction (KI) domain. We further show that during brain development, hnRNPK expression becomes more and more restricted to granule cells of the cerebellum and hippocampal neurons where it localizes in the cell nucleus as well as in the spine/dendritic compartment. The downregulation of hnRNPK in cultured hippocampal neurons by RNAi results in an enlarged dendritic tree and a significant increase in filopodia formation. This is accompanied by a decrease in the number of mature synapses. Both effects therefore mimic the neuronal morphology after downregulation of Abi-1 mRNA in neurons.
  
  
  CONCLUSIONS
  Our findings demonstrate a novel interplay between hnRNPK and Abi-1 in the nucleus and at synaptic sites and show obvious similarities regarding both protein knockdown phenotypes. This indicates that hnRNPK and Abi-1 act synergistic in a multiprotein complex that regulates the crucial balance between filopodia formation and synaptic maturation in neurons.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Proepper
authors.forename: Konrad
authors.initials: K
authors.lastname: Steinestel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmeisser
authors.forename: Jutta
authors.initials: J
authors.lastname: Heinrich
authors.forename: Julie
authors.initials: J
authors.lastname: Steinestel
authors.forename: Juergen
authors.initials: J
authors.lastname: Bockmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebau
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000502:physiology*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D041681:NIH 3T3 Cells; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011554:Pseudopodia / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D013569:Synapses / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: C554931:Abi1 protein, rat; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034741:RNA, Small Interfering
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