Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes

Michael E. Cahill, Zhong Xie, Michelle Day, Maria V. Barbolina, Courtney A. Miller, Craig Weiss, Jelena Radulovic, J. David Sweatt, John F. Disterhoft, D. James Surmeier, Peter Penzes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


Dendritic spine morphogenesis contributes to brain function, cognition, and behavior, and is altered in psychiatric disorders. Kalirin is a brain-specific guanine-nucleotide exchange factor (GEF) for Rac-like GTPases and is a key regulator of spine morphogenesis. Here, we show that KALRN-knockout mice have specific reductions in cortical, but not hippocampal, Rac1 signaling and spine density, and exhibit reduced cortical glutamatergic transmission. These mice exhibit robust deficits in working memory, sociability, and prepulse inhibition, paralleled by locomotor hyperactivity reversible by clozapine in a kalirin-dependent manner. Several of these deficits are delayed and age-dependent. Our study thus links spine morphogenic signaling with age-dependent, delayed, disease-related phenotypes, including cognitive dysfunction.

Original languageEnglish (US)
Pages (from-to)13058-13063
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 4 2009


  • Alzheimer's disease
  • Antipsychotic
  • Prefrontal cortex
  • Schizophrenia
  • Synaptic plasticity

ASJC Scopus subject areas

  • General


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