title: An SK3 channel/nWASP/Abi-1 complex is involved in early neurogenesis.
abstract: BACKGROUND
  The stabilization or regulated reorganization of the actin cytoskeleton is essential for cellular structure and function. Recently, we could show that the activation of the SK3-channel that represents the predominant SK-channel in neural stem cells, leads to a rapid local outgrowth of long filopodial processes. This observation indicates that the rearrangement of the actin based cytoskeleton via membrane bound SK3-channels might selectively be controlled in defined micro compartments of the cell.
  
  
  RESULTS
  We found two important proteins for cytoskeletal rearrangement, the Abelson interacting protein 1, Abi-1 and the neural Wiskott Aldrich Syndrome Protein, nWASP, to be in complex with SK3- channels in neural stem cells (NSCs). Moreover, this interaction is also found in spines and postsynaptic compartments of developing primary hippocampal neurons and regulates neurite outgrowth during early phases of differentiation. Overexpression of the proteins or pharmacological activation of SK3 channels induces obvious structural changes in NSCs and hippocampal neurons. In both neuronal cell systems SK3 channels and nWASP act synergistic by strongly inducing filopodial outgrowth while Abi-1 behaves antagonistic to its interaction partners.
  
  
  CONCLUSIONS
  Our results give good evidence for a functional interplay of a trimeric complex that transforms incoming signals via SK3-channel activation into the local rearrangement of the cytoskeleton in early steps of neuronal differentiation involving nWASP and Abi-1 actin binding proteins.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebau
authors.forename: Julie
authors.initials: J
authors.lastname: Steinestel
authors.forename: Leonhard
authors.initials: L
authors.lastname: Linta
authors.forename: Alexander
authors.initials: A
authors.lastname: Kleger
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.forename: Michael
authors.initials: M
authors.lastname: Schoen
authors.forename: Konrad
authors.initials: K
authors.lastname: Steinestel
authors.forename: Christian
authors.initials: C
authors.lastname: Proepper
authors.forename: Juergen
authors.initials: J
authors.lastname: Bockmann
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmeisser
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D015640:Ion Channel Gating / Q000187:drug effects; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism*
chemical_list: C554931:Abi1 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D001562:Benzimidazoles; D002227:Carbazoles; C496901:Kcnn3 protein, rat; D046912:Multiprotein Complexes; D011412:Propanolamines; D051640:Small-Conductance Calcium-Activated Potassium Channels; C495770:Wasl protein, rat; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C489942:wiskostatin; D001030:Apamin; C102635:1-ethyl-2-benzimidazolinone