Induction of spine growth and synapse formation by regulation of the spine actin cytoskeleton

Karen Zito, Graham Knott, Gordon M G Shepherd, Shirish Shenolikar, Karel Svoboda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

We explored the relationship between regulation of the spine actin cytoskeleton, spine morphogenesis, and synapse formation by manipulating expression of the actin binding protein NrbI and its deletion mutants. In pyramidal neurons of cultured rat hippocampal slices, NrbI is concentrated in dendritic spines by binding to the actin cytoskeleton. Expression of one NrbI deletion mutant, containing the actin binding domain, dramatically increased the density and length of dendritic spines with synapses. This hyperspinogenesis was accompanied by enhanced actin polymerization and spine motility. Synaptic strengths were reduced to compensate for extra synapses, keeping total synaptic input per neuron constant. Our data support a model in which synapse formation is promoted by actin-powered motility.

Original languageEnglish (US)
Pages (from-to)321-334
Number of pages14
JournalNeuron
Volume44
Issue number2
DOIs
StatePublished - Oct 14 2004

Funding

We thank Barry Burbach, John Wallach, and Catherine Zhang for help with experiments; Tom Pologruto and Volker Scheuss for programming; Carey Oliver and Ryan Terry-Lorenzo for sharing data and reagents prior to publication; and Vincenzo De Paola, Ingrid Ehrlich, Anthony Holtmaat, and Alla Karpova for critical reading of the manuscript. This work was supported by the Helen Hay Whitney Foundation (K.Z. was a Merck Fellow), a Burroughs Wellcome Fund Career Award (K.Z.), the Swiss National Science Foundation (G.K.), HHMI (G.M.G.S. and K.S.), and NIH (K.S.).

ASJC Scopus subject areas

  • General Neuroscience

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