Kalirin Regulates Cortical Spine Morphogenesis and Disease-related Behavioral Phenotypes

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Jul 24

PMID 19625617

Citations 107

Authors

Michael E Cahill

Zhong Xie

Michelle Day

Huzefa Photowala

Maria V Barbolina

Courtney A Miller

Craig Weiss

Jelena Radulovic

J David Sweatt

John F Disterhoft

D James Surmeier

Peter Penzes

Affiliations

Soon will be listed here.

Abstract

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.

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