Metabotropic glutamate receptors (mGluRs): structure and coupling to G proteins

摘要

Glutamate mediates transmission at most central excitatory synapses. The modulation of synaptic activity of those synapses is responsible for several forms of plasticity involved in learning and memory [1]. Excessive release of glutamate has been implicated in acute, as well as in slow neuronal death associated with pathologies such as ischemia, epilepsy, Parkinson's disease, amyotrophic lateral slerosis, Huntington's chorea and Alzheimer's disease [2,3]. Fifteen years ago, our conception of synaptic activation of glutamate receptors was simply explained by fast postsynaptic currents generated by AMPA receptor channels and a slower response generated by calcium-permeable NMDA receptor channels. Today, the glutamatergic synaptic transmission appears more complex (fig. 1). Firstly, the synaptic ionotropic glutamate receptors have recently been joined by kainate receptors [4,5]. All these ionotropic receptors are composed of a large number of subunits and spliced variants (fig. 2). Their subsynaptic localization and function can be modified following their interaction with associated proteins (such as SAP 95) and phosphorylation, respectively (for a review see [6]).