SLC1A2

Fig1. Caspase-3 cleavage occurs at a conserved consensus site within the cytosolic c-terminus domain of EAAT2. (Emily Foran, 2013)

What is SLC1A2 protein?

SLC1A2 (solute carrier family 1 member 2) gene is a protein coding gene which situated on the short arm of chromosome 11 at locus 11p13. This gene encodes a member of a family of solute transporter proteins which is also called EATT2. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. SLC1A2 protein is consisted of 574 amino acids and its molecular mass is approximately 62.1 kDa.

What is the function of SLC1A2 protein?

EAAT2 is responsible for the reuptake of glutamate from the synaptic cleft into glial cells and neurons. This process is essential for preventing excitotoxicity, which can occur if glutamate accumulates and overstimulates its receptors. By transporting glutamate back into cells, EAAT2 helps to maintain the balance of glutamate in the brain, which is critical for proper neuronal signaling and preventing neuronal damage. EAAT2 contributes to neuroprotection by clearing excess glutamate, which can be toxic to neurons in high concentrations. EAAT2 is involved in neuronal development and synaptic plasticity. Glutamate taken up by EAAT2 can be used in glial cells for energy production, which is important for brain metabolism and the maintenance of the blood-brain barrier.

SLC1A2 Related Signaling Pathway

The SLC1A2 signaling pathway is involved in the regulation of several biological processes, including cell proliferation, differentiation, and apoptosis. In addition to its role in maintaining redox balance, SLC1A2 is also involved in the regulation of other signaling pathways, including the PI3K/Akt and MAPK/ERK pathways. It can interact with various signaling molecules, including growth factor receptors, kinases, and transcription factors, to regulate the activity of these pathways.

SLC1A2 Related Diseases

SLC1A2 is overexpressed in many types of cancer, including breast cancer, lung cancer, and gastric cancer. It has been shown that SLC1A2 plays a critical role in the growth and survival of cancer cells by regulating the redox balance of cells. SLC1A2 is involved in the regulation of glutamate homeostasis in the brain. SLC1A2 is involved in the regulation of oxidative stress in the heart. SLC1A2 has also been implicated in the development of other diseases such as inflammatory bowel disease, rheumatoid arthritis, and diabetes mellitus.

Bioapplications of SLC1A2

SLC1A2 is overexpressed in many types of cancer, including breast cancer, lung cancer, and gastric cancer. By targeting SLC1A2, drugs can be developed to inhibit the growth and survival of cancer cells. SLC1A2 has also been implicated in the development of other diseases such as inflammatory bowel disease, rheumatoid arthritis, and diabetes mellitus. By targeting SLC1A2, drugs can be developed to treat these diseases.

Case Study 1: Amanda L Sheldon, 2008

The objective of this study was to investigate the ubiquitination mediated internalization and degradation of glutamate transporter GLT-1 in astrocytes. Using C6 glioma cells or primary cortical cultures, the research team showed that activation of protein kinase C (PKC) leads to the binding of ubiquitin in GLT-1 immunoprecipitate. By mutation analysis, lysine residues at the carboxyl terminus of GLT-1 were found to be essential for PKC-mediated GLT-1 internalization and degradation. Studies have shown that redundant lysine residues at the carboxyl terminus are sufficient to enable ubiquitination products to appear and lead to degradation of GLT-1. These findings define a new mechanism by which a major glutamate transporter in the prefrontal lobe of the brain can be rapidly targeted for degradation.

Fig1. C6 cells were transiently transfected with GLT-1 or GLT-1 (K-R) mutant transporter cDNAs and treated with vehicle (DMSO) or PMA.

Fig2. Effect of PMA on cell surface expression of GLT-1 (K-R) mutant transporters.

Case Study 2: Eva Perez-Jimenez, 2021

Lafora disease (LD) is a rare and fatal form of progressive myoclonus epilepsy that typically manifests during early adolescence. The underlying cause of the disease is mutations in the EPM2A or EPM2B genes, which encode laforin and malin respectively. While the exact roles of laforin and malin are not fully understood, it is known that they function as a complex, with laforin recruiting targets for ubiquitination by malin. Recent studies have suggested that the type of epilepsy associated with LD may be due to deficiencies in the function of the astrocytic glutamate transporter GLT-1. In mouse models of LD, astrocytes were found to have decreased levels of GLT-1 at the plasma membrane, leading to increased levels of glutamate in the brain parenchyma. This study found that the absence of a functional laforin/malin complex (as seen in LD cellular models) results in altered ubiquitination of GLT-1, which could be the cause of the reduced levels of GLT-1 at the plasma membrane. Conversely, overexpression of the laforin/malin complex promotes the retention of GLT-1 at the plasma membrane.

Fig3. Analysis of the levels of GLT-1 at the plasma membrane by flow cytometry.

Fig4. Decreased ubiquitination of GLT-1 in LD primary astrocytes.

SLC1A2 has several biochemical functions, for example, L-glutamate transmembrane transporter activity,glutamate:sodium symporter activity,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SLC1A2 itself. We selected most functions SLC1A2 had, and list some proteins which have the same functions with SLC1A2. You can find most of the proteins on our site.

SLC1A2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SLC1A2 here. Most of them are supplied by our site. Hope this information will be useful for your research of SLC1A2.

MAPT;GRB2