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Regulation of Glutamate Transporter Expression in Glial Cells

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Glial Amino Acid Transporters

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 16))

Abstract

Glutamate (Glu) is the major excitatory neurotransmitter in the vertebrate central nervous system. During synaptic activity, Glu is released into the synaptic cleft and binds to Glu receptors activating a wide variety of signal transduction cascades. Extracellular Glu concentrations are maintained exclusively within physiological levels mainly by glial Glu transporters. Inefficient clearance of synaptic Glu may be neurotoxic owing to prolonged hyperactivation of postsynaptic Glu receptors, causing a multitude of intracellular events in the postsynaptic neuron, which ultimately results in neuronal cell death. This phenomenon is known as excitotoxicity and is the underlying mechanisms of a number of neurodegenerative diseases. Therefore, it is important to understand the regulation of Glu transporters’ function. Transporter activity can be regulated in different ways, including gene expression, transporter protein targeting and trafficking, and posttranslational modifications of the transporter protein. The identification of these mechanisms has allowed to understand the role of Glu transporters during pathology and will aid in the development of therapeutic strategies for treating or preventing pathologies associated with excitotoxicity.

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Abbreviations

ATP:

Adenosine triphosphate

dbcAMP:

Dibutyryl cyclic adenosine monophosphate

CNS:

Central nervous system

DNA:

Deoxyribonucleic acid

EAAC1:

Excitatory amino acid carrier 1

EAAT:

Excitatory amino acid transporters

EGF:

Epidermal growth factor

GLAST:

Glutamate/aspartate transporter

GLT-1:

Glutamate transporter 1

Glu:

Glutamate

Gln:

Glutamine

GSH:

Glutathione

GTRP:

Glutamate transporter-associated protein

mRNA:

Messenger ribonucleic acid

NCM:

Neuron-conditioned media

NF-κB:

Nuclear factor-kappa B

NGF:

Nerve growth factor

PACAP:

Pituitary adenylate cyclase-activating peptide

PI3K:

Phosphoinositide 3-kinase

PKA:

Protein kinase A

PKC:

Protein kinase C

SLC1 :

Solute carrier 1 gene

TGFα:

Transforming growth factor alpha

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Acknowledgments

The work in the laboratory is supported by Conacyt-Mexico (255087) and Soluciones para un México Verde S.A. de C.V.; Donají Chi-Castañeda and Edna Suárez-Pozos are supported by Conacyt-México fellowships (376687 and 232180, respectively).

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The author declares no conflicts of interest.

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  1. Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, Ciudad de México, 07000, México

    Donají Chi-Castañeda, Edna Suárez-Pozos & Arturo Ortega

  2. Soluciones para un México Verde S.A. de C.V., Ciudad de México, 01210, México

    Donají Chi-Castañeda

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  1. Donají Chi-Castañeda
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Correspondence to Arturo Ortega .

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  1. Department of Toxicology, Cinvestav-IPN México City, México, Mexico

    Arturo Ortega

  2. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

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Chi-Castañeda, D., Suárez-Pozos, E., Ortega, A. (2017). Regulation of Glutamate Transporter Expression in Glial Cells. In: Ortega, A., Schousboe, A. (eds) Glial Amino Acid Transporters. Advances in Neurobiology, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-55769-4_10

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