Kalirin loss results in cortical morphological alterations

Zhong Xie, Michael E. Cahill, Peter Penzes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Morphogenesis of pyramidal neuronal dendrites and spines is crucial for the formation and refinement of forebrain neuronal circuits underlying cognition. Aberrant dendrite and spine morphology is associated with neuropathological disorders. However, the molecular mechanisms controlling pyramidal neuronal dendrite and spine morphogenesis in vivo remain largely unknown. Kalirin is a brain-specific guanine-nucleotide exchange factor for Rho-like small GTPases, and an important regulator of spine morphogenesis in cultured neurons. Here we show that RNAi-dependent knockdown of kalirin in cultured neurons affected dendrite morphology. Cortical pyramidal neurons from KALRN-null mice showed reduced spine density and impaired activity-dependent spine plasticity; and they exhibited reduced complexity of dendritic trees. KALRN-null mice also displayed smaller neuronal cell bodies and reductions in the size of the cortex and cortical layers. These data demonstrate important roles for kalirin in the regulation of cortical structure, ultrastructure, and spine structural plasticity.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume43
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Dendrites
  • Dendritic spine
  • KALRN
  • Knockout
  • Prefrontal cortex
  • Rac1
  • Small GTPase
  • Synaptic plasticity

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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