| First Author | Kerrisk ME | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 16 | Pages | 6742-52 |
| PubMed ID | 23595732 | Mgi Jnum | J:196653 |
| Mgi Id | MGI:5488992 | Doi | 10.1523/JNEUROSCI.0528-13.2013 |
| Citation | Kerrisk ME, et al. (2013) Integrin alpha3 is required for late postnatal stability of dendrite arbors, dendritic spines and synapses, and mouse behavior. J Neurosci 33(16):6742-52 |
| abstractText | Most dendrite branches and a large fraction of dendritic spines in the adult rodent forebrain are stable for extended periods of time. Destabilization of these structures compromises brain function and is a major contributing factor to psychiatric and neurodegenerative diseases. Integrins are a class of transmembrane extracellular matrix receptors that function as alphabeta heterodimers and activate signaling cascades regulating the actin cytoskeleton. Here we identify integrin alpha3 as a key mediator of neuronal stability. Dendrites, dendritic spines, and synapses develop normally in mice with selective loss of integrin alpha3 in excitatory forebrain neurons, reaching their mature sizes and densities through postnatal day 21 (P21). However, by P42, integrin alpha3 mutant mice exhibit significant reductions in hippocampal dendrite arbor size and complexity, loss of dendritic spine and synapse densities, and impairments in hippocampal-dependent behavior. Furthermore, gene-dosage experiments demonstrate that integrin alpha3 interacts functionally with the Arg nonreceptor tyrosine kinase to activate p190RhoGAP, which inhibits RhoA GTPase and regulates hippocampal dendrite and synapse stability and mouse behavior. Together, our data support a fundamental role for integrin alpha3 in regulating dendrite arbor stability, synapse maintenance, and proper hippocampal function. In addition, these results provide a biochemical and structural explanation for the defects in long-term potentiation, learning, and memory reported previously in mice lacking integrin alpha3. |
