title: Inositol-1,4,5-trisphosphate-3-kinase-A controls morphology of hippocampal dendritic spines.
abstract: Long-lasting synaptic plasticity is often accompanied by morphological changes as well as formation and/or loss of dendritic spines. Since the spine cytoskeleton mainly consists of actin filaments, morphological changes are primarily controlled by actin binding proteins (ABPs). Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) is a neuron-specific, actin bundling protein concentrated at dendritic spines. Here, we demonstrate that ITPKA depletion in mice increases the number of hippocampal spine-synapses while reducing average spine length. By employing actin to ABP ratios similar to those occurring at post synaptic densities, in addition to cross-linking actin filaments, ITPKA strongly inhibits Arp2/3-complex induced actin filament branching by displacing the complex from F-actin. In summary, our data show that in vivo ITPKA negatively regulates formation and/or maintenance of synaptic contacts in the mammalian brain. On the molecular level this effect appears to result from the ITPKA-mediated inhibition of Arp2/3-complex F-actin branching activity.
authors.affiliation: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Jan-Dietrich
authors.initials: JD
authors.lastname: Köster
authors.affiliation: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Birthe
authors.initials: B
authors.lastname: Leggewie
authors.affiliation: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Blechner
authors.affiliation: Department of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Brandt
authors.affiliation: Department of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Fester
authors.affiliation: Department of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rune
authors.affiliation: Center for Molecular Neurobiology Hamburg, Falkenried 94, D-20251 Hamburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schweizer
authors.affiliation: Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kindler
authors.affiliation: Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. Electronic address: s.windhorst@uke.uni-hamburg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Windhorst
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D013569:Synapses / Q000378:metabolism*
chemical_list: D000199:Actins; D053496:Inositol 1,4,5-Trisphosphate Receptors
keywords: Arp2/3 complex; Cytoskeleton; Drebrin; ITPKA; Neurons; Synaptic plasticity