| First Author | Warren MS | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 8 | Pages | 2824-34 |
| PubMed ID | 22357865 | Mgi Jnum | J:182501 |
| Mgi Id | MGI:5315777 | Doi | 10.1523/JNEUROSCI.3942-11.2012 |
| Citation | Warren MS, et al. (2012) Integrin beta1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior. J Neurosci 32(8):2824-34 |
| abstractText | 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 beta1 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 beta1 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 beta1 signaling through Arg recapitulate the integrin beta1 knock-out phenotype in a gene dose-sensitive manner. Together, these results describe a novel integrin beta1-Arg-p190RhoGAP pathway that regulates dendritic arbor size, promotes synapse maintenance, supports proper hippocampal function, and mitigates the behavioral consequences of cocaine exposure. |
