Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines

Zhong Xie, Deepak P. Srivastava, Huzefa Photowala, Li Kai, Michael E. Cahill, Kevin M. Woolfrey, Cassandra Y. Shum, D. James Surmeier, Peter Penzes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

265 Scopus citations

Abstract

Activity-dependent rapid structural and functional modifications of central excitatory synapses contribute to synapse maturation, experience-dependent plasticity, and learning and memory and are associated with neurodevelopmental and psychiatric disorders. However, the signal transduction mechanisms that link glutamate receptor activation to intracellular effectors that accomplish structural and functional plasticity are not well understood. Here we report that NMDA receptor activation in pyramidal neurons causes CaMKII-dependent phosphorylation of the guanine-nucleotide exchange factor (GEF) kalirin-7 at residue threonine 95, regulating its GEF activity, leading to activation of small GTPase Rac1 and rapid enlargement of existing spines. Kalirin-7 also interacts with AMPA receptors and controls their synaptic expression. By demonstrating that kalirin expression and spine localization are required for activity-dependent spine enlargement and enhancement of AMPAR-mediated synaptic transmission, our study identifies a signaling pathway that controls structural and functional spine plasticity.

Original languageEnglish (US)
Pages (from-to)640-656
Number of pages17
JournalNeuron
Volume56
Issue number4
DOIs
StatePublished - Nov 21 2007

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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