The mammalian solute carrier family 1 contains five high affinity, Na +-dependent glutamate transporters and two structurally related Na+-dependent, neutral amino acid transporters. The SLC1 transporters are presumed to be structurally similar given their almost identical hydrophobicity profiles and membrane topologies. Many of the expected features were observed in the crystal structure generated from the glutamate transporter homolog, GltPh from Pyrococcus horikoshii. The structure features a bowl-shaped trimer containing an aqueous basin facing the extracellular solution and extending halfway through the membrane bilayer. Each monomer consists of eight α-helical transmembrane segments and two helical hairpins. While these transporters have similar structural properties, they are functionally distinct. Mammalian glutamate transporters take up 1 L-Glu, L-Asp, or D-Asp molecule along with 3 Na+ and 1 H+, in exchange for 1 K+, whereas the neutral amino acid transporters instead mediate Na+-dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr. The regulated action of glutamate transporters permits normal excitatory neurotransmission and protects neurons from overstimulation by glutamate. Excitotoxic damage to neurons has been implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's, and Huntington's and ischemia, for example after a stroke or a head injury.
|Title of host publication||Handbook of Neurochemistry and Molecular Neurobiology|
|Subtitle of host publication||Neural Membranes and Transport|
|Number of pages||19|
|Publication status||Published - 1 Dec 2007|
|MoE publication type||A3 Part of a book or another research book|