A latest study from National Centre for Biological Sciences (NCBS-TIFR) has proposed that a key protein found in the brain can act as a natural smart sensor hinting at impending neurodegeneration in cells. The study was conducted by Professor Raghu Padinjat’s group and published in the Journal of Cell Biology.
Cells in the brain need to communicate and stay updated about the developments and all ongoing activities within its neighbourhood in order to support the brain and bodily functions. But how is it accomplished? The exterior region of a cell constitutes the plasma membrane (PM) and endoplasmic reticulum (ER). The region where their ER-PM boundaries meet are known as the Membrane Contact Sites (MCS). These sites facilitate intra-cellular signalling, transport of essentials like lipids and calcium between organelles and are vital for cell health. Whereas, PM is responsible mainly for maintaining two-way communication of the cell and filtering material into the cell.
Recent research has identified around 20 proteins at MCS, but their specific roles in maintaining cell health remain an active area of study.
Padinjat’s lab at NCBS had, previously, shown how the presence of Retinal Degeneration B (RDGB) – an essential protein sitting at the MCS. Back then, researchers had concluded that the absence of RDGB blinded the flies. In other words, the MCS density depended on the incoming light intensity.
Aimed at advancing the scope of understanding the importance of MCS and the role of calcium in their new study, researchers tracked how some of these proteins found near MCS regulated cell functioning at this site. With the help of the Drosophila fly model, researchers observed the changes in the photoreceptors (light sensitive neurons in the fly’s retina) when they were subjected to visible light during the experiment. The calcium present at MCS monitors the incoming light and signals the cells to undertake lipid transfers.
In the process, the team identified a new protein named Extended synaptotagmin (Esyt) at MCS which is the first to sense the variation in the calcium levels and instantly signal the same to the cells. It possesses a C2 domain that has the ability to bind and detect calcium.
“Esyt’s strategic presence at the contact site allows it to first decode the calcium binding to the C2 domain. Loss of this ability makes the cell incapable of adjusting its functioning to the varying light intensities,” said Raghu Padinjat, professor and senior author of the study.
Healthy and adequate number of MCS are essential for cell functioning. It is the calcium which signals to the cells if there is a need for creating more MCS, thereby ensuring continuous lipid transfer into the cell, said Vaisaly Nath, lead author of the study.
Researchers said that Esyt could be used as a smart sensor that can point to the onset of neurodegeneration in cells. “Esyt monitors incoming light and accordingly signals the cells in the fly’s eyes to adapt its working machinery. A failure in this signalling could result in the onset of loss of cell structure, commonly referred to, with respect to the brain, as neurodegeneration. And in case of the Drosophila fly, it suffered retinal degeneration,” said Padinjat.
Link to the study: https://rupress.org/jcb/article/224/5/e202407190/277301/Ca2-binding-to-E...
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