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

Pascate Chavis, Gary Westbrook

Research output: Contribution to journalArticle

264 Citations (Scopus)

Abstract

Coordinated signalling between presynaptic terminals and their postsynaptic targets is essential for the development and function of central synapses. In addition to diffusible molecules, this bidirectional flow of information could involve direct interactions through cell-adhesion molecules. 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-eGly-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.

Original languageEnglish (US)
Pages (from-to)317-321
Number of pages5
JournalNature
Volume411
Issue number6835
DOIs
StatePublished - May 17 2001
Externally publishedYes

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Integrins
Synapses
Cell Adhesion Molecules
Synaptotagmin I
Antibodies
Presynaptic Terminals
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Binding Sites
Peptides

ASJC Scopus subject areas

  • General

Cite this

Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse. / Chavis, Pascate; Westbrook, Gary.

In: Nature, Vol. 411, No. 6835, 17.05.2001, p. 317-321.

Research output: Contribution to journalArticle

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