Homer as Both a Scaffold and Transduction Molecule

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Science's STKE  18 Jun 2002:
Vol. 2002, Issue 137, pp. re8
DOI: 10.1126/stke.2002.137.re8

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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.