TY - JOUR T1 - Integrin β1 Signals through Arg to Regulate Postnatal Dendritic Arborization, Synapse Density, and Behavior JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2824 LP - 2834 DO - 10.1523/JNEUROSCI.3942-11.2012 VL - 32 IS - 8 AU - M. Sloan Warren AU - William D. Bradley AU - Shannon L. Gourley AU - Yu-Chih Lin AU - Mark A. Simpson AU - Louis F. Reichardt AU - Charles A. Greer AU - Jane R. Taylor AU - Anthony J. Koleske Y1 - 2012/02/22 UR - http://www.jneurosci.org/content/32/8/2824.abstract N2 - Integrins are heterodimeric extracellular matrix receptors that are essential for the proper development of the vertebrate nervous system. We report here that selective loss of integrin β1 in excitatory neurons leads to reductions in the size and complexity of hippocampal dendritic arbors, hippocampal synapse loss, impaired hippocampus-dependent learning, and exaggerated psychomotor sensitivity to cocaine in mice. Our biochemical and genetic experiments demonstrate that the intracellular tail of integrin β1 binds directly to Arg kinase and that this interaction stimulates activity of the Arg substrate p190RhoGAP, an inactivator of the RhoA GTPase. Moreover, genetic manipulations that reduce integrin β1 signaling through Arg recapitulate the integrin β1 knock-out phenotype in a gene dose-sensitive manner. Together, these results describe a novel integrin β1–Arg–p190RhoGAP pathway that regulates dendritic arbor size, promotes synapse maintenance, supports proper hippocampal function, and mitigates the behavioral consequences of cocaine exposure. ER -