Glutamate transporters: Critical components of glutamatergic transmission

Glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system. Once released, it binds to specific membrane receptors and transporters activating a wide variety of signal transduction cascades, as well as its removal from the synaptic cleft in order to avoid its extracellular accumulation and the overstimulation of extra-synaptic receptors that might result in neuronal death through a process known as excitotoxicity. Although neurodegenerative diseases are heterogenous in clinical phenotypes and genetic etiologies, a fundamental mechanism involved in neuronal degeneration is excitotoxicity. Glutamate homeostasis is critical for brain physiology and Glutamate transporters are key players in maintaining low extracellular Glutamate levels. Therefore, the characterization of Glutamate transporters has been an active area of glutamatergic research for the last 40 years. Transporter activity its regulated at different levels: transcriptional and translational control, transporter protein trafficking and membrane mobility, and through extensive post-translational modifications. The elucidation of these mechanisms has emerged as an important piece to shape our current understanding of glutamate actions in the nervous system.

Automated summary

Glutamate is a major excitatory neurotransmitter in the central nervous system, and its dysregulation can lead to excitotoxicity and neuronal death. Glutamate transporters play a crucial role in maintaining low extracellular glutamate levels through various regulatory mechanisms such as transcriptional, translational, protein trafficking, and post-translational modifications. Understanding these mechanisms is essential in shaping our current knowledge of glutamate actions in the nervous system.