References

154 T. Müller, W. Koch, D. Wipf
11.2
Amino Acid Transport in Animals
TheproteinsinvolvedinAAtransportarefoundinatleastsevensolute
carrier families (SLC): SLC7, SLC17, SLC32, SLC36 and SLC38 are phylogenetically
related to plant transport systems, whereas no homologs to SLC1
and SLC6 could be found in the Arabidopsis genome.
11.2.1
Sodium Dicarboxylate Symporter Family (SDS, SLC1)
The SLC1 family comprises five high-affinity glutamate transporters (system
X− AG )SLCA1 (EAAC1, EAAT3),SLC1A2 (GlT1,EAAT2), SLC1A3 (GLAST,
EAAT1), SLC1A6 (EAAT4) and SLC1A7 (EAAT5) and two neutral AA transporters
(system ASC) SLC1A4 (ASCT1, SATT) and SLC1A5 (ASCT2, AAAT,
hATB0) (Kanai and Hediger 2004). Uptake of glutamate is coupled with
cotransport of three sodium ions, one proton and the countertransport of
one potassium ion (Fig. 11.1) (Zerangue and Kavanaugh 1996). This coupling
makes the transport against a concentration gradient more powerful
and speeds up the removal of excitatory AA from the synaptic cleft and
in the surrounding neuroglia, protecting neurons against accumulation to
neurotoxic levels (Fig. 11.1) (Kanai and Hediger 2004). The glutamate transporter
EAAC1 was also shown to facilitate substrate exchange (Kanai and
Hediger 2004). SLC1 members regularly have ten transmembrane domains
with cytosolic C- and N- termini (Wipf et al. 2002). Recently Kanai and
Hediger (2004) developed a membrane model of glutamate transporters
with eight predicted transmembrane domains, a large extracellular glycosylatedloopandareentrantloop(twoshorterhydrophobicdomains)
between domains 7 and 8, similar to the ion-permeating pore of ion channels.
The neutral AA transporter isoforms (ASCT1 and ASCT2; Fig. 11.1)
transport L-alanine, L-serine, L-cysteine and L-threonine with high affinity
in dependency to sodium ions. In addition to these substrates, ASCT2
also has a high affinity to glutamine and asparagine and a lower affinity
to methionine, leucine and glycine (Kanai and Hediger 2004). One of the
main functions of ASC transporters is the exchange of AA, but they can also
act as ligand-gated ion channels without being combined with potassium
countertransport and proton cotransport (Broer et al. 2000; Zerangue and
Kavanaugh 1996). Most SLC1 members are found in brain tissues although
representatives of system B0 (Lynch and McGivan 1987), ASC (Vadgama
and Christensen 1984), ASCT1 and ASCT2 (Zerangue and Kavanaugh 1996)
and X− AG have also been found in nonbrain tissues (Wipf et al. 2002). For