Solute Carrier Family 1

Over the past decade, we have made exciting progress in the understanding of the physiology, pathology, and pharmacology of members of the solute carrier family 1 (SLC1), including high-affinity glutamate and neutral amino acid transporters. Glutamate transporters play a critical role in terminating excitatory neurotransmission and providing cells throughout the body with glutamate for metabolic purposes. The high-affinity glutamate transporters SLC1A1, SLC1A2, SLC1A3, SLC1A6, and SLC1A7 protect the CNS from glutamate-induced neurotoxicity. Glutamate transporters not only play a key role in the central nervous system by keeping extracellular levels below neurotoxic levels but also in peripheral tissues. For example, they contribute to nitrogen metabolism and inter-organ glutamine flux. In the central nervous system, glutamate transporters are found to be involved in neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. The glutamate transporter also plays a key role in neuronal damage associated with ischemia. These findings make glutamate transporters potential drug targets.

Fig.1 Membrane topology and transport mechanism model of mammalian glutamate transporters. (Kanai, 2013)

In mammals, the SLC1 family includes five high-affinity glutamate transporters and two neutral amino acid transporters. Here show the six members of the SLC1 family of solute carriers: three excitatory amino acid transporters (SLC1A1, SLC1A2 and SLC1A3), two neutral amino acid transporters (SLC1A4 and SLC1A5) and an excitatory amino acid transporter (SLC1A7). In humans, the five glutamate transporters possess 44-55% amino acid sequence identity with each other, while the two amino acid transporters show 57% identity with each other.

Human SLC1 Family Members
SLC1A1	SLC1A2	SLC1A3	SLC1A4	SLC1A5	SLC1A7

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Reference

Kanai Y, et al. (2013). The SLC1 high-affinity glutamate and neutral amino acid transporter family. Mol Aspects Med. 34(2-3): 108-20.

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