CNS Neurons Deposit Laminin ?5 to Stabilize Synapses.

ABSTRACT: Synapses in the developing brain are structurally dynamic but become stable by early adulthood. We demonstrate here that an ?5-subunit-containing laminin stabilizes synapses during this developmental transition. Hippocampal neurons deposit laminin ?5 at synapses during adolescence as connections stabilize. Disruption of laminin ?5 in neurons causes dramatic fluctuations in dendritic spine head size that can be rescued by exogenous ?5-containing laminin. Conditional deletion of laminin ?5 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 ?5 acts through an integrin ?3?1-Abl2 kinase-p190RhoGAP signaling cascade and partners with laminin ?2 to regulate dendritic spine density and behavior. Together, our results identify laminin ?5 as a stabilizer of dendritic spines and synapses in the brain and elucidate key cellular and molecular mechanisms by which it acts.

SUBMITTER: Omar MH 

PROVIDER: S-EPMC5776391 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature