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Synaptic localization and activity of ADAM10 regulate excitatory synapses through N-cadherin cleavage

, : Synaptic localization and activity of ADAM10 regulate excitatory synapses through N-cadherin cleavage. Journal of Neuroscience 30(48): 16343-16355

N-Cadherin has an important role during dendrite arborization, axon guidance, and synaptogenesis. In particular, at synaptic sites, N-cadherin is involved in the regulation of cell-cell adhesion and in morphology and plasticity control. Recent studies have shown that N-cadherin can be cleaved by the metalloproteinase ADAM10. Here we demonstrate that impairing ADAM10 localization and activity at synaptic sites decreases its processing of N-cadherin. This leads to an accumulation of the full-length form of N-cadherin, to an increase in spine head width, and to modifications of the number and function of glutamate receptors of AMPA type, both in vitro and in vivo. Our results indicate a key role for ADAM10 in the complex sequence of events through which N-cadherin affects spine maturation and controls structure and function of glutamatergic synapses.


PMID: 21123580

DOI: 10.1523/JNEUROSCI.1984-10.2010

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