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Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse

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  • Pascale Chavis

    (Vollum Institute Oregon Health Sciences, University Portland
    CNRS UPR 9023)

  • Gary Westbrook

    (Vollum Institute Oregon Health Sciences, University Portland)

Abstract

Coordinated signalling between presynaptic terminals and their postsynaptic targets is essential for the development and function of central synapses. In addition to diffusible molecules1, this bidirectional flow of information could involve direct interactions through cell-adhesion molecules2,3. Here, we show that one class of cell-adhesion molecule, the integrins, are required for the functional maturation of hippocampal synapses in vitro. At immature synapses, a high probability of glutamate release (Pr) was correlated with the expression of postsynaptic NMDA (N-methyl-D-aspartate) receptors containing the NR2B subunit. The activity-dependent reduction in Pr and a switch in the subunit composition of synaptic NMDA receptors was prevented by chronic blockade with peptides containing the integrin-binding site Arg-Gly-Asp (RGD), or by a functional antibody against the β3 integrin subunit. Active synapses, monitored by the uptake of antibodies against the intraluminal domain of synaptotagmin I, also had β3 subunit immunoreactivity. Our results provide evidence that integrin-mediated signalling is essential for the orchestrated maturation of central excitatory synapses.

Suggested Citation

  • Pascale Chavis & Gary Westbrook, 2001. "Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse," Nature, Nature, vol. 411(6835), pages 317-321, May.
    • Handle: RePEc:nat:nature:v:411:y:2001:i:6835:d:10.1038_35077101
    DOI: 10.1038/35077101
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    Cited by:

    1. David M Santucci & Sridhar Raghavachari, 2008. "The Effects of NR2 Subunit-Dependent NMDA Receptor Kinetics on Synaptic Transmission and CaMKII Activation," PLOS Computational Biology, Public Library of Science, vol. 4(10), pages 1-16, October.

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