Résumé
Increasing evidence shows that scaffold proteins not only control membrane assembly of receptors and channels, but also modulate intracellular signaling by assembled receptors. The Homer family of proteins act as scaffolds to bind clusters of proteins and glutamate receptors at postsynaptic sites. We review results of cloning and gene expression of this protein family, and summarize roles in glutamate receptor function and intracellular signaling in neurons. Homer proteins trigger the localization of metabotropic glutamate receptor subtype 5 (mGlu5 receptor) to the postsynaptic plasma membrane. They can also alter the kinetics and peak amplitude of the intracellular Ca
2+
responses of mGlu1 and mGlu5 receptors. Homer proteins can either prevent or promote spontaneous activation of these receptors, depending on the type of Homer protein isoform expressed.
Glutamate is the major excitatory neurotransmitter of the mammalian brain. It activates two types of synaptic receptors: ionotropic receptor-channels and metabotropic heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The ionotropic glutamate receptors generate fast postsynaptic responses, whereas the metabotropic glutamate (mGlu) receptors modulate these fast responses, generate slower postsynaptic potentials, or both. Glutamatergic synaptic transmission depends on the adequate localization and intracellular signaling of these postsynaptic receptors and channels. This is achieved by scaffolding proteins that assemble glutamate receptors into functional complexes at postsynaptic membranes. However, little is known about the role of these intracellular proteins in the receptor signaling. A new family of proteins that interact with mGlu receptors has been cloned from rat brain and named Homer or Ves1 proteins. We review recent data indicating that Homer proteins not only control expression and localization of mGlu receptors and channels, but also participate in signaling of glutamate receptors in neurons.