SLC1A1 Membrane Protein Introduction

Introduction of SLC1A1

SLC1A1, also known as excitatory amino acid transporter 3 (EAAT3), is a protein encoded by the SLC1A1 gene. Solute carrier family 1 member 1 is a member of high-affinity glutamate transporters that play a crucial role in the delivery of glutamate. In the brain, excitatory amino acid transporters are critical in terminating the postsynaptic effects of the neurotransmitter glutamate and maintaining extracellular glutamate levels below neurotoxicity levels. SLC1A1 also transports Aspartate, and mutation of SLC1A1 gene that is thought to cause dicarboxylic acidosis, also known as glutamine-aspartate transport defects. SLC1A1 protein is also the main pathway for neuronal absorption. Cysteine is a component of the major antioxidant glutathione, and mice lacking SLC1A1 show reduced glutathione levels in neurons, increased oxidative stress, and age-related neuronal loss, especially Melanin neurons.

Function of SLC1A1 Protein

Excitatory amino acid transporter 3 (EAAT3), known as excitatory amino acid carrier 1 (EAAC1), represents a major neuronal member of the excitatory amino acid transport family, including EAATs 1-5. EAAT3 is mainly expressed in the hippocampus, followed by the cerebral cortex, striatum and thalamus. More specifically, the highest level of transcription of EAAT3 in mice is seen in the pyramidal layer of the hippocampus, CA1 to CA4, and the granule layer of the dentate gyrus, where it is widely distributed in all neurons. The EAAT3 protein has three major physiological functions: 1) uptake of synaptic glutamate, preventing glutamate from active synapses from spilling into the exogenous region; 2) providing glutamate as a precursor for gamma aminobutyric acid (GABA) synthesis; 3) Neuronal absorption of cysteine neurons, synthesis of intracellular glutathione (GSH) rate-limiting matrix in neurons.

Fig.1 The structure of SLC1A1 Protein.

Application of SLC1A1 Protein in Literature

1. Afshari P., et al. Reduced Slc1a1 expression is associated with neuroinflammation and impaired sensorimotor gating and cognitive performance in mice: Implications for schizophrenia. PLoS ONE. 2017, 12(9): e0183854. PubMed ID: 28886095.
   
   

   These results suggest that partial loss of the mouse SLC1A1 gene results in haploinsufficiency associated with behavioral, histological, and biochemical changes that reflect an altered redox state and may promote behavioral characteristics and inflammation. The expression of the state is consistent with the observation of schizophrenia.

2. Afshari P., et al. Characterization of a Novel Mutation in SLC1A1 Associated with Schizophrenia. Molecular Neuropsychiatry. 2015, 1 (3): 125–144. PubMed ID: 26380821.
   
   

   The new findings revealed that the Sequence Upstream of Exon 2 promotes transcription of 5′-Truncated SLC1A1.

3. Zike I. D., et al. OCD Candidate Gene SLC1A1/EAAT3 Impacts Basal Ganglia-Mediated Activity and Stereotypic Behavior. Proceedings of the National Academy of Sciences of the United States of America.2017,114 (22): 5719–5724. PubMed ID: 28507136
   
   

   These findings provide evidence that SLC1A1 affects basal ganglia-dependent repetitive behavior and suggests potential targets for drug development.

4. Wei Y. B., et al. MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro. International Journal of Neuropsychopharmacology. 2016,19 (12): pyw069. PubMed ID: 27507301.
   
   

   The authors found that miR-101b targets the neuronal glutamate transporter SLC1A1 by using a combination of in silico and in vitro analyses.

5. Beaudin S., Welsh J. 1,25-Dihydroxyvitamin D induces the glutamate transporter SLC1A1 and alters glutamate handling in non-transformed mammary cells. Molecular and cellular endocrinology. 2016, (424):34-41. PubMed ID: 26774511.
   
   

   This article reveals that SLC1A1 has been upregulated 3-fold within 4 h of 1,25D-treatment, suggesting that SLC1A1 may be a direct target of the 1,25D-VDR complex.

SLC1A1 Preparation Options

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