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Cell Rep. 2017 Oct 31;21(5):1281-1292. doi: 10.1016/j.celrep.2017.10.028.

CNS Neurons Deposit Laminin α5 to Stabilize Synapses.

Author information

1
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA.
3
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06510, USA.
4
Department of Ophthalmology, Upstate Medical University, Syracuse, NY 13202, USA.
5
Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA; Department of Neuroscience, Yale University, New Haven, CT 06510, USA; Department of Neurosurgery, Yale University, New Haven, CT 06510, USA.
7
Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06510, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06510, USA; Department of Neuroscience, Yale University, New Haven, CT 06510, USA. Electronic address: anthony.koleske@yale.edu.

Abstract

Synapses in the developing brain are structurally dynamic but become stable by early adulthood. We demonstrate here that an α5-subunit-containing laminin stabilizes synapses during this developmental transition. Hippocampal neurons deposit laminin α5 at synapses during adolescence as connections stabilize. Disruption of laminin α5 in neurons causes dramatic fluctuations in dendritic spine head size that can be rescued by exogenous α5-containing laminin. Conditional deletion of laminin α5 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 α5 acts through an integrin α3β1-Abl2 kinase-p190RhoGAP signaling cascade and partners with laminin β2 to regulate dendritic spine density and behavior. Together, our results identify laminin α5 as a stabilizer of dendritic spines and synapses in the brain and elucidate key cellular and molecular mechanisms by which it acts.

KEYWORDS:

ECM; Lama5; Lamb2; adhesion; extracellular matrix; motility; stability; structural plasticity; synapse loss; synapse maturation

PMID:
29091766
PMCID:
PMC5776391
DOI:
10.1016/j.celrep.2017.10.028
[Indexed for MEDLINE]
Free PMC Article

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