Neurobiology of glycine transporters: From molecules to behavior

  • Neurosci Biobehav Rev. 2020 Nov:118:97-110. doi: 10.1016/j.neubiorev.2020.07.025.
Bruno Lemes Marques  1 ,  Onésia Cristina Oliveira-Lima  1 ,  Gustavo Almeida Carvalho  1 ,  Raphaela de Almeida Chiarelli  1 ,  Raul Izidoro Ribeiro  1 ,  Ricardo Cambraia Parreira  1 ,  Elis Marra da Madeira Freitas  1 ,  Rodrigo Ribeiro Resende  2 ,  Friederike Klempin  3 ,  Henning Ulrich  4 ,  Renato Santiago Gomez  5 ,  Mauro Cunha Xavier Pinto  6
Affiliations
  • 1. Laboratório de Neuroquímica e Neurofarmacologia - Neurolab, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, GO, Brazil.
  • 2. Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 3. Max Delbrück Center for Molecular Medicine, Berlin, Germany.
  • 4. Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
  • 5. Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • 6. Laboratório de Neuroquímica e Neurofarmacologia - Neurolab, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, GO, Brazil. Electronic address: [email protected].
PMID: 32712279 DOI: 10.1016/j.neubiorev.2020.07.025
Abstract

Glycine transporters (GlyTs) are Na+/Cl--dependent neurotransmitter transporters, responsible for l-glycine uptake into the central nervous system. GlyTs are members of the solute carrier family 6 (SLC6) and comprise glycine transporter type 1 (SLC6A9; GlyT1) and glycine transporter type 2 (SLC6A5; GlyT2). GlyT1 and GlyT2 are expressed on both astrocytes and neurons, but their expression pattern in brain tissue is foremost related to neurotransmission. GlyT2 is markedly expressed in brainstem, spinal cord and cerebellum, where it is responsible for glycine uptake into glycinergic and GABAergic terminals. GlyT1 is abundant in neocortex, thalamus and hippocampus, where it is expressed in astrocytes, and involved in glutamatergic neurotransmission. Consequently, inhibition of GlyT1 transporters can modulate glutamatergic neurotransmission through NMDA receptors, suggesting an alternative therapeutic strategy. In this review, we focus on recent progress in the understanding of GlyTs role in brain function and in various diseases, such as epilepsy, hyperekplexia, neuropathic pain, drug addiction, schizophrenia and stroke, as well as in neurodegenerative disorders.

Keywords
Glutamatergic neurotransmission and glycine neurotransmission; GlyT1; GlyT2; Glycine transporters.