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A more recent version of this article appeared on March 9, 2007
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M610981200v1
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Papers In Press, published online ahead of print January 9, 2007
J. Biol. Chem, 10.1074/jbc.M610981200
Submitted on November 29, 2006
Accepted on January 9, 2007

alpha 5 integrin signaling regulates the formation of spines and synapses in hippocampal neurons

Donna J. Webb, Huaye Zhang, Devi Majumdar, and Alan F. Horwitz

Biological Sciences, Vanderbilt University, Nashville, TN 37235

Corresponding Author: donna.webb{at}vanderbilt.edu

The actin based dynamics of dendritic spines play a key role in synaptic plasticity, which underlies learning and memory. While it is becoming increasingly clear that modulation of actin is critical for spine dynamics, the upstream molecular signals that regulate the formation and plasticity of spines are poorly understood. In nonneuronal cells, integrins are critical modulators of the actin cytoskeleton, but their function in the nervous system is not well characterized. Here we show that alpha 5 integrin regulates spine morphogenesis and synapse formation in hippocampal neurons. Knockdown of alpha 5 integrin expression using siRNA decreased the number of dendritic protrusions, spines, and synapses. Expression of constitutively active or dominant negative alpha 5 integrin also resulted in alterations in the number of dendritic protrusions, spines, and synapses. alpha 5 integrin signaling regulates spine morphogenesis and synapse formation by a mechanism that is dependent on Src kinase, Rac, and the signaling adaptor, GIT1. Alterations in the activity or localization of these molecules result in a significant decrease in the number of spines and synapses. Thus, our results point to a critical role for integrin signaling in regulating the formation of dendritic spines and synapses in hippocampal neurons.


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