Structure-Function Relationship of Transporters in the Glutamate-Glutamine Cycle of the Central Nervous System

Int J Mol Sci. 2018 Apr 12;19(4):1177. doi: 10.3390/ijms19041177.

Abstract

Many kinds of transporters contribute to glutamatergic excitatory synaptic transmission. Glutamate is loaded into synaptic vesicles by vesicular glutamate transporters to be released from presynaptic terminals. After synaptic vesicle release, glutamate is taken up by neurons or astrocytes to terminate the signal and to prepare for the next signal. Glutamate transporters on the plasma membrane are responsible for transporting glutamate from extracellular fluid to cytoplasm. Glutamate taken up by astrocyte is converted to glutamine by glutamine synthetase and transported back to neurons through glutamine transporters on the plasma membranes of the astrocytes and then on neurons. Glutamine is converted back to glutamate by glutaminase in the neuronal cytoplasm and then loaded into synaptic vesicles again. Here, the structures of glutamate transporters and glutamine transporters, their conformational changes, and how they use electrochemical gradients of various ions for substrate transport are summarized. Pharmacological regulations of these transporters are also discussed.

Keywords: astrocyte; glutamate transporter; glutamine transporter; neuron; vesicular glutamate transporter.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Central Nervous System / metabolism*
  • Cytoplasm / metabolism
  • Extracellular Fluid / metabolism
  • Glutamic Acid / metabolism
  • Glutamine / metabolism*
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Structure-Activity Relationship
  • Synaptic Transmission
  • Synaptic Vesicles / metabolism
  • Vesicular Glutamate Transport Proteins / chemistry*
  • Vesicular Glutamate Transport Proteins / metabolism*

Substances

  • Carrier Proteins
  • Vesicular Glutamate Transport Proteins
  • glutamine transport proteins
  • Glutamine
  • Glutamic Acid