NCBS study identifies key protein whose dysfunction could trigger neurodegenerative diseases

Confocal microscopy image depicting the localisation of the calcium-binding mutant of Esyt in Drosophila photoreceptors, along side the contact site marker RDGB and phalloidin labeling F-actin
| Photo Credit: SPECIAL ARRANGEMENT

Neurobiologists from the National Centre for Biological Sciences (NCBS-TIFR) have identified a key protein whose dysfunction could potentially trigger neurodegenerative diseases.

Using the Drosophila model, the group led by Professor Raghu Padinjat has identified a protein named Extended synaptotagmin (Esyt) that sits close to the cell membrane. The study was published in the Journal of Cell Biology.

According to NCBS, a cell’s exterior region comprises plasma membrane(PM) and endoplasmic reticulum (ER).

Outer boundary

PM forms the cell’s outer boundary, gatekeeping entry of material into the cell and communicating between the outside of the cell and its interior, whereas the ER is a network of membranes inside the cell. The region where PM and ER meet is known as the membrane contact site (MCS). This site permits intra-cellular signalling, transporting essentials like lipids and calcium between organelles.

“Over the past decade or so, modern genomics and technological advancements have helped scientists establish that more than 20 proteins are located at the MCS between the ER and PM. However, there is still limited scientific evidence to answer why certain proteins are prevalent at these sites or what role they play in cell health,” NCBS said.

The present study has tracked how some of these proteins tune the operations at the cell MCS, whose health is directly linked to cell health.

Calcium’s role

NCBS said for photoreceptors, a special type of neuron in the retina, calcium is a message encoder. It encodes and delivers information (about light intensity) from the surroundings to the cell, which in this case is the amount of light. When light is absorbed, the lipid transfer activity of RDGB at MCS is triggered. As lipids are exhausted, this stock needs to be replenished.

“It will happen only when calcium is effectively able to communicate this to the cell. This means that the cell needs to stay informed about its surroundings, which we think is being done by the changes in intracellular calcium,” said Raghu Padinjat, Professor, NCBS.

Taking this research a step ahead with the newly identified protein Esyt, researchers said that it possesses a C2 domain that can bind and detect calcium. Loss of the ability to bind calcium by the C2 domain of Esyt makes the cell incapable of adjusting its MCS function in response to illumination.