New views of glutamate transporter structure and function: Advances and challenges

Neuronal and glial glutamate transporters limit the action of excitatory amino acids after their release during synaptic transmission. Recent structural and functional investigations have revealed much about the transport and conducting mechanisms of members of the sodium-coupled symporter family responsible for glutamate clearance in the nervous system. In this review we summarize emerging views on the general structure, binding sites for substrates and coupled ions, and transport mechanisms of mammalian glutamate transporters, integrating results from a large body of work on carrier structure–function relationships with several crystal structures obtained for the archaeal ortholog, GltPh.