First Author | Omar MH | Year | 2017 |
Journal | Cell Rep | Volume | 21 |
Issue | 5 | Pages | 1281-1292 |
PubMed ID | 29091766 | Mgi Jnum | J:254944 |
Mgi Id | MGI:6103988 | Doi | 10.1016/j.celrep.2017.10.028 |
Citation | Omar MH, et al. (2017) CNS Neurons Deposit Laminin alpha5 to Stabilize Synapses. Cell Rep 21(5):1281-1292 |
abstractText | Synapses in the developing brain are structurally dynamic but become stable by early adulthood. We demonstrate here that an alpha5-subunit-containing laminin stabilizes synapses during this developmental transition. Hippocampal neurons deposit laminin alpha5 at synapses during adolescence as connections stabilize. Disruption of laminin alpha5 in neurons causes dramatic fluctuations in dendritic spine head size that can be rescued by exogenous alpha5-containing laminin. Conditional deletion of laminin alpha5 in vivo increases dendritic spine size and leads to an age-dependent loss of synapses accompanied by behavioral defects. Remaining synapses have larger postsynaptic densities and enhanced neurotransmission. Finally, we provide evidence that laminin alpha5 acts through an integrin alpha3beta1-Abl2 kinase-p190RhoGAP signaling cascade and partners with laminin beta2 to regulate dendritic spine density and behavior. Together, our results identify laminin alpha5 as a stabilizer of dendritic spines and synapses in the brain and elucidate key cellular and molecular mechanisms by which it acts. |