Ninjurin-1 proteins put together (green/yellow) into filaments and burst the cell membrane (gray) till the cell breaks down entirely. “We are now fixing how the cells actually rupture. Instead of rupturing like a balloon, the protein ninjurin-1 supplies a breaking point in the cell membrane, causing rupture at particular websites.”
Rather, a specific protein serves as a breaking point for the cell membrane rupture. In this way, the cell membrane is cleaved open piece by piece up until the cell breaks down completely.”
Ninjurin-1 proteins assemble (green/yellow) into filaments and rupture the cell membrane (gray) till the cell breaks down entirely. Intracellular parts are revealed in blue. Credit: Biozentrum, University of Basel
In our bodies, millions of cells fulfill their end on an everyday basis. Contrary to popular belief, cells do not simply blow up when they die.
The self-elimination of cells is an important process for all living organisms. When cells end up being damaged or infected with infections or germs, they start an internal “self-destruct” sequence. This important mechanism wards off the possible development of growths and prevents the spread of hazardous pathogens throughout the body.
Up until just recently, it was assumed that cells just break and die at the end of their life. Now, researchers at the Biozentrum of the University of Basel, the University of Lausanne, and the Department of Biosystems Science and Engineering (D-BSSE) at ETH Zurich have supplied new insights into the last step of cell death.
In the clinical journal Nature, they explain how a protein called ninjurin-1 puts together into filaments that work like a zipper and open the cell membrane, thus causing the disintegration of the cell. The brand-new insights are an essential milestone in the understanding of cell death.
Protein serves as a snapping point in the cell membrane.
Various signals, such as bacterial parts, set off the cell death equipment. At the final stage of this process, the cells protective membrane is jeopardized by tiny pores which allow ions to stream into the cell.
” The typical understanding was that the cell then swells up until it lastly bursts due to increasing osmotic pressure,” explains Professor Sebastian Hiller who heads a research group at the Biozentrum, University of Basel. “We are now dealing with how the cells really rupture. Rather of breaking like a balloon, the protein ninjurin-1 provides a breaking point in the cell membrane, causing rupture at specific websites.”
At the end of their lives, cells do not just burst. Instead, a particular protein functions as a breaking point for the cell membrane rupture. SNI PhD trainee Morris Degen (Biozentrum, University of Basel) explains how this system works. Credit: Swiss Nanoscience Institute
Using innovative methods such as highly delicate microscopic lens and NMR spectroscopy, the scientists have been able to clarify the mechanism by which ninjurin-1 induces membrane rupture at the level of individual atoms. Ninjurin-1 is a small protein embedded in the cell membrane.
” Upon receiving the suicide command, 2 ninjurin-1 proteins at first cluster together and drive a wedge into the membrane,” describes Morris Degen, very first author of the study and Ph.D. student at the Ph.D. In this way, the cell membrane is cleaved open piece by piece until the cell breaks down completely.”
The cell particles is then gotten rid of by the bodys own cleaning service.
” It is now obvious that the cells do not burst without ninjurin-1. They do swell to a particular level due to the influx of ions, but membrane rupture is contingent on the function of this protein,” adds Hiller. “The books chapter on cell death will be expanded with these lovely structural insights.”
Treatment to prevent or promote cell death
A much deeper understanding of cell death will facilitate the search for unique drug targets. Restorative interventions to treat cancer are imaginable since some tumor cells avert configured cell death.
Also, when it comes to premature cell death observed in neurodegenerative diseases such as Parkinsons disease or in lethal conditions such as septic shock, drugs that interfere in this procedure are a possible treatment option.
Referral: “Structural basis of NINJ1-mediated plasma membrane rupture in cell death” by Morris Degen, José Carlos Santos, Kristyna Pluhackova, Gonzalo Cebrero, Saray Ramos, Gytis Jankevicius, Ella Hartenian, Undina Guillerm, Stefania A. Mari, Bastian Kohl, Daniel J. Müller, Paul Schanda, Timm Maier, Camilo Perez, Christian Sieben, Petr Broz and Sebastian Hiller, 17 May 2023, Nature.DOI: 10.1038/ s41586-023-05991-z.