Glutamate aspartate transporter

Glutamate Aspartate Transporter (GLAST), also known as Excitatory Amino Acid Transporter 1 (EAAT1), is a protein that in humans is encoded by the SLC1A3 gene. It is one of the key glutamate transporters involved in the regulation of glutamate levels in the central nervous system (CNS). Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system, and its precise regulation is vital for preventing neurotoxicity due to excessive accumulation. GLAST plays a crucial role in this regulatory process, primarily in the astrocytes, which are a type of glial cell in the brain.

Function

The primary function of the Glutamate Aspartate Transporter is to remove glutamate from the synaptic cleft and maintain it at low concentrations in the extracellular space, thus ensuring proper synaptic function and preventing excitotoxicity. GLAST, along with other glutamate transporters such as GLT-1 (EAAT2), is responsible for the uptake of glutamate into astrocytes, where glutamate is either stored or converted into glutamine via the enzyme glutamine synthetase. Glutamine can then be supplied to neurons and converted back into glutamate or GABA, thus completing the glutamate-glutamine cycle.

Clinical Significance

Alterations in the expression or function of GLAST have been implicated in various neurological disorders, including amyotrophic lateral sclerosis (ALS), epilepsy, and ischemic stroke. In conditions such as ischemic stroke, the failure of glutamate transporters to effectively remove glutamate from the extracellular space can lead to increased levels of glutamate, causing excitotoxicity and neuronal death.

Genetic Aspects

The SLC1A3 gene encoding the Glutamate Aspartate Transporter is located on chromosome 5p13. Mutations in this gene have been associated with episodic ataxia type 6 (EA6), a rare neurological condition characterized by episodes of ataxia, seizures, and migraine. This highlights the importance of GLAST in maintaining the balance of excitatory neurotransmission and its role in neurological health.

Research Directions

Research on GLAST is ongoing, with studies focusing on understanding its structure, function, and regulation at a molecular level. Insights into the mechanisms regulating GLAST expression and activity could lead to new therapeutic targets for treating neurological disorders associated with glutamate dysregulation.