Fellow’s research: Brain receptor’s “dance” is tuned by sugars present on its surface


12 Sep 2019

Fellow’s research: Brain receptor’s “dance” is tuned by sugars present on its surface

 

Dr Janesh Kumar, Intermediate Fellow

National Centre for Cell Science, Pune

Our recently published study provides insights into the various movements underlying functions of GluK3 receptor, an important brain receptor that helps nerve cells communicate with each other. We also show that sugar molecules present on the receptor surface fine-tune the crucial brain signalling carried out of these receptors.

Typical functions of the brain depend on the ability of nerve cells to transmit electrical signals. GluK3 receptor belongs to the family of glutamate receptor ion channels that are fundamentally involved in this electrical transmission in the brain. These receptors underlie a multitude of high cognitive functions, including learning and memory, and their malfunction is implicated in a remarkable range of diseases of the nervous system such as Alzheimer's, Parkinson's, epilepsy, and schizophrenia. Hence, it is critical to understand how they operate and how their functions are regulated.

Towards this goal, we trapped the GluK3 receptor in two different states of its back-and-forth motions (gating cycle) and determined their structure via high-powered electron microscopy. The comparison and analysis of the structures revealed the various movements (dance) of the receptor responsible for its functions. Using the structures as a guide and by recording the electrical activity of multiple variants of the receptor, we show that the sugar chains that are present on the receptor surface mediate interactions between various regions of the receptor and tune its properties.

Our results provide the first 3D view of GluK3 receptor and provide evidence that sugars present on its surface, fine-tune the organized back-and-forth motions of the receptor. This detailed view gives critical clues to developing drugs for combating several neurological diseases and conditions. It is invaluable as efforts are ongoing around the world to develop drugs that might work on specific receptor types that may help fight some of the neurological disorders.

Schematic representation of the receptor in two states of its activity. Sugar chains present on its surface that tune its properties are shown by red lines.

References:

Structural and functional insights into GluK3-kainate receptor desensitization and recovery. Jyoti Kumari, Rajesh Vinnakota, Janesh Kumar. Scientific Reports. July 2019