Details

Autor(en) / Beteiligte

• Köster, Jan-Dietrich
• Leggewie, Birthe
• Blechner, Christine
• Brandt, Nicola
• Fester, Lars
• Rune, Gabriele
• Schweizer, Michaela
• Kindler, Stefan
• Windhorst, Sabine

Titel

Inositol-1,4,5-trisphosphate-3-kinase-A controls morphology of hippocampal dendritic spines

Ist Teil von

• Cellular signalling, 2016-01, Vol.28 (1), p.83-90

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •ITPKA controls morphology of dendritic spines of hippocampal neurons•ITPKA negatively regulates the number of spine synapses•ITPKA inhibits Arp2/3 complex dependent F-actin branches at concentrations occurring at PSD•ITPKA-mediated reduction of F-actin branches contributes to regulate stability of synaptic contacts