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-Gly-Asp (RGD), or by a functional antibody against the beta3 integrin subunit. Active synapses, monitored by the uptake of antibodies against the intraluminal domain of synaptotagmin I, also had beta3 subunit immunoreactivity. Our results provide evidence that integrin-mediated signalling is essential for the orchestrated maturation of central excitatory synapses.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / metabolism
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Calcium-Binding Proteins*
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Cell Adhesion / drug effects
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Cells, Cultured
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Genistein / pharmacology
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Glutamic Acid / metabolism
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Hippocampus / cytology*
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Hippocampus / metabolism*
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Integrin beta3
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Integrins / antagonists & inhibitors
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Integrins / metabolism*
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Intercellular Signaling Peptides and Proteins
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Isoflavones / pharmacology
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Membrane Glycoproteins / metabolism
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Models, Neurological
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Nerve Tissue Proteins / metabolism
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Oligopeptides / metabolism
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Oligopeptides / pharmacology
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Peptides / pharmacology
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Platelet Membrane Glycoproteins / antagonists & inhibitors
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Platelet Membrane Glycoproteins / metabolism
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Protein Subunits
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Quinazolines
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / chemistry
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Receptors, N-Methyl-D-Aspartate / metabolism
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Signal Transduction / drug effects
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Synapses / drug effects
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Synapses / metabolism*
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Synaptotagmin I
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Synaptotagmins
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Tyrphostins / pharmacology
Substances
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Antigens, CD
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Calcium-Binding Proteins
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Excitatory Amino Acid Antagonists
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Integrin beta3
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Integrins
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Intercellular Signaling Peptides and Proteins
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Isoflavones
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Membrane Glycoproteins
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Nerve Tissue Proteins
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Oligopeptides
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Peptides
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Platelet Membrane Glycoproteins
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Protein Subunits
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Quinazolines
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Receptors, N-Methyl-D-Aspartate
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Synaptotagmin I
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Tyrphostins
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echistatin
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Synaptotagmins
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RTKI cpd
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Glutamic Acid
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daidzein
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arginyl-glycyl-aspartic acid
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Genistein