References

156 T. Müller, W. Koch, D. Wipf
11.2.2
The Sodium- and Chloride-Dependent Neurotransmitter
Transporter Family (NTF, SLC6)
Members of the neurotransmitter superfamily (SLC6) are key regulators of
extracellular neurotransmitter levels and are necessary for normal neurotransmission
(Fig. 11.1) (Melikian 2004). SLC6 transporters (e.g., γaminobutyric
acid, GABA, transporters GAT1-3, Fig. 11.1, dopamine transporter,
DAT, etc.) regulate the level of extracellular solute concentrations
and are mainly found in the central and peripheral nervous system (Chen
et al. 2004) where they are involved in the signalling pathway. They are,
however, also found in many nonneural tissues with diverse physiological
functions. For example, SLC6A6 (taurine transporter, TAUT) and SLC6A12
(betaine transporter, BGT1) take part in osmoregulation in kidney (Chen
et al. 2004). Genes of the SLC6 family encode proteins of approximately
600 AA with a common structure of 12 transmembrane domains with predicted
intracellular N- and C-termini (Nelson 1998). The solute transport
is coupled with the cotransport of Na + and Cl − .Thetransportofneurotransmitter
molecules against the concentration gradient uses energy
produced by the electrochemical Na + gradient (Chen et al. 2004; Wipf et
al. 2002). Na + is absolutely necessary for transport activities in contrast to
Cl − , whose requirement for cotransport varies across members (Chen et
al. 2004). Most of the SLC6 members are regulated by protein kinases, although
some other mechanisms are assumed to exist (Blakely and Bauman
2000). In organisms like yeasts, fungi and plants, that do not typically use
Na + gradients for metabolite uptake, no homologs to the SLC6 family could
be found (Saier 1999).
11.2.3
Cationic Amino Acid Transporters and Heteromeric
Amino Acid Transporters (SLC7)
The SLC7 family is divided into two subgroups: cationic AA transporters
(CAT) (SLC7A1–4) and heteromeric AA transporters (HAT) (SLC7A5–11).
Members of the CAT subgroup have 14 putative transmembrane domains
and are found in both animals and plants (Wipf et al. 2002). Mammalian
CATs mediate Na + -independent uptake of cationic AA (Closs et al. 1993).
Transport properties of the CAT are those of system y + .Thesecondsubgroup
(HAT) comprises proteins with 12 putative transmembrane domains.
In contrast to what was observed for the CAT members, HAT transporters
are quite diverse in terms of substrate selectivity, transporting neutral L-
AA (large and small), negatively charged AA and cationic AA plus neutral