‘The First 3-D Model of GluD1 Receptor’

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.

 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.