| Literature References | 1. ATTELL, D. AND MOBBS, P.
Neurotransmitter transporters.
CURR.OPIN.NEUROBIOL. 4 353-359 (1994).
2. MALANDRO, M.S. AND KILBERG, M.S.
Molecular biology of mammalian amino acid transporters.
ANNU.REV.BIOCHEMISTRY 65 305-336 (1996).
3. AMARA, S.G. AND ARRIZA, J.L.
Neurotransmitter transporters: three distinct gene families.
CURR.OPIN.NEUROBIOL. 3 337-344 (1993).
4. UHL, G.R. AND JOHNSON, P.S.
Neurotransmitter transporters: Three important gene families for neuronal
function.
J.EXP.BIOL. 196 229-236 (1994).
5. LILL, H. AND NELSON, N.
Homologies and family relationships among Na+/Cl- neurotransmitter
transporters.
METHODS ENZYMOL. 306 425-436 (1998).
6. BECK, F.X., SCHMOLKE, M. AND GUDER, W.G.
Osmolytes.
CURR.OPIN.NEPHROL.HYPERTENS. 1 43-52 (1992).
7. UCHIDA, S., KWON, H.M., YAMAUCHI, A., PRESTON, A.S., MARUMO, F.
AND HANDLER, J.S.
Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(-)-dependent
taurine transporter that is regulated by hypertonicity.
PROC.NATL.ACAD.SCI.U.S.A. 89 8230-8234 (1992).
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| Documentation | Neurotransmitter transport systems are integral to the release, re-uptake
and recycling of neurotransmitters at synapses. High affinity tranport
proteins found in the plasma membrane of presynaptic nerve terminals and
glial cells are responsible for the removal from the extracellular space
of released-transmitters, thereby terminating their actions [1]. Plasma
membrane neurotransmitter transporters fall into two structurally and
mechanistically distinct families. The majority of the transporters
constitute an extensive family of homologous proteins that derive energy
from the co-transport of Na+ and Cl-, in order to transport neurotransmitter
molecules into the cell against their concentration gradient. The family
has a common structure of 12 presumed transmembrane helices and includes
carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline,
dopamine, serotonin, proline, glycine, choline, betaine and taurine. They
are structurally distinct from the second more-restricted family of plasma
membrane transporters, which are responsible for excitatory amino acid
tranport. The latter couple glutamate and aspartate uptake to the co-
transport of Na+ and the counter-transport of K+, with no apparent
dependence on Cl- [2]. In addition, both of these transporter families
are distinct from the vesicular neurotransmitter transporters [3,4].
Sequence analysis of the Na+/Cl- neurotransmitter superfamily reveals that
it can be divided into four subfamilies, these being transporters for
monoamines, the amino acids proline and glycine, GABA, and a group of
orphan transporters [5].
Cells regulate their volume and adapt to alterations in the tonicity of
their local environment by adjusting their solute content accordingly.
Resultant water movements rapidly establish osmotic balance. Solutes
utilised in this manner are referred to as osmolytes and include: glycero-
phosphorylcholine, betaine, myo-inositol, sorbitol and taurine [6].
Cell membrane transporters for betaine and taurine have been cloned, and by
sequence similarity they have been shown to belong to the Na+ and Cl-
-coupled neurotransmitter transporter superfamily. The taurine transporter
has a predicted length of ~620 amino acids and can also transport beta-
alanine. It has been found to be widely distributed in the body, with
transcripts being detected in the kidney (high abundance), ileal mucosa,
liver, heart and in several regions of the brain including: the corpus
callosum, striatum and anterior commisure. Functional studies have
revealed that taurine transporter activity is regulated by hypertonicity,
and this regulation appears to occur at the level of mRNA accumulation [7].
TAUTRANSPORT is a 4-element fingerprint that provides a signature for
taurine transporters. The fingerprint was derived from an initial alignment
of 5 sequences: the motifs were drawn from conserved regions spanning
virtually the full alignment length, focusing on those sections that
characterise the taurine transporter but distinguish it from others - motif
1 resides within the putative cytoplasmic N-terminus; motif 2 encodes a
short stretch of the large extracellular loop located between putative TM
domains 3 and 4; and motifs 3-4 lie within the putative cytoplasmic
C-terminus. A single iteration on SPTR37_9f was required to reach convergence,
no further sequences being identified beyond the starting set.
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