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‘The First 3-D Model of GluD1 Receptor’

  • Category
    Internal Security
  • Published
    21st Jan, 2020

Researchers at the Department of Biotechnology’s Pune-based National Centre for Cell Science (NCCS) have captured ‘three-dimensional views’ of a protein called ‘GluD1 receptor’. 

Context

Researchers at the Department of Biotechnology’s Pune-based National Centre for Cell Science (NCCS) have captured ‘three-dimensional views’ of a protein called ‘GluD1 receptor’. 

What are GluD1 receptors?

  • GluD1 receptor is a subtype of a family of proteins called glutamate receptors.
  • Simply put, GluD1 is a protein that in humans is encoded by the GRID1 gene.
  • Several studies have shown a strong association between several variants of the GRID1 gene and increased risk of developing schizophrenia.
  • It is a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons.
  • GluD1 is selectively required for the formation of inhibitory synapses and regulates GABAergic synaptic transmission accordingly.

On Glutamate:

  • Glutamate is the most abundant neurotransmitter in our brain and central nervous system (CNS).
  • It is involved in virtually every major excitatory brain function. Glutamate is also a metabolic precursor for another neurotransmitter called GABA (gamma-aminobutyric acid).
  • ABA is the main inhibitory neurotransmitter in the central nervous system.
  • Glutamate receptors play crucial roles in motor coordination and motor learning, high-frequency hearing and are also key to many other brain functions.
  • Besides, they are linked to social and cognitive deficits and neuronal disorders like Schizophrenia and cocaine addiction.

Neurological disorders are diseases of the central and peripheral nervous system. In other words, the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscles. These disorders include epilepsy, Alzheimer disease and other dementias, cerebrovascular diseases including stroke, migraine and other headache disorders, multiple sclerosis, Parkinson's disease, neuro infections, brain tumours, traumatic disorders of the nervous system.

 What has been founded?

  • The researchers found that GluD1 receptors had an unprecedented domain organisation, distinct from that observed in other members of the glutamate receptor family.
  • This shows that glutamate receptor ion channels are all not built the same way.
  • Majority (60 percent) of excitatory brain signalling is carried out by glutamate receptor ion channels that are present on the synaptic junctions of neurons.
  • Interestingly, while many other members of the family of glutamate receptor are activated by neurotransmitter glutamate binding, GluD1 receptors are not.
  • This is a new discovery and could provide deeper insights into the molecular underpinnings of receptor functions.

How they did it?

  • The researchers had complexed the receptor with ligands that stabilised it to ensure that it was visualised well.
  • This was critical as the inherent conformational variations limit the details that could be observed otherwise.
  • They used the Cryo-EM technique that images several thousand molecules in a frozen state and combines the 2D images generated to build a three-dimensional view.

Significance of the discovery:

  • Understanding nervous system disorders: This new discovery offers clues into the structural difference that might offer some unique insight into the mechanism behind a wide range of nervous system disorders and diseases.
  • A platform to discover treatments: The study has created a robust platform for understanding the functions of GluD1 and developing therapeutics to treat neurological disorders that are associated with GluD1 dysfunction.
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