New insights into cell death reveal how a protein works like a zipper to open cell membranes

Scientists from the University of Basel, in collaboration with researchers from the University of Lausanne and ETH Zurich, have made a groundbreaking discovery regarding cell death. Contrary to the previous belief that cells simply burst at the end of their lifespan, they have identified a specific protein called ninjurin-1 that plays a crucial role in this process. By examining the atomic level mechanism, the scientists have revealed that ninjurin-1 forms filaments resembling a zipper, causing the cell membrane to rupture and leading to the breakdown of the cell. This discovery, published in the esteemed journal Nature, marks a significant advancement in our understanding of cell death. It sheds light on the intricate mechanisms that enable damaged cells or those infected with pathogens to initiate a self-destruct program, preventing the formation of tumors and impeding the spread of harmful agents within the body.

Protein acts as a breaking point in the cell membrane

Cell death is initiated by various signals, such as components from bacteria, which activate the cell death machinery. During the final stage of this process, the integrity of the cell’s protective membrane is compromised by the formation of small pores, enabling the influx of ions into the cell. Previously, it was widely believed that the cell would swell until it reached a point of bursting due to increased osmotic pressure. However, Professor Sebastian Hiller, who leads a research group at the Biozentrum, University of Basel, explains that their recent findings challenge this understanding. Instead of the cell bursting like a balloon, the protein ninjurin-1 has been identified as a critical factor in creating specific sites of rupture in the cell membrane, acting as a breaking point. This revelation provides valuable insights into the actual process of cell rupture, marking a significant departure from the previously held concept.

Credit: University of Basel

By employing advanced techniques like highly sensitive microscopes and NMR spectroscopy, the scientists have successfully unraveled the intricate mechanism through which ninjurin-1 triggers membrane rupture at the atomic level. Ninjurin-1 is a small protein that resides within the cell membrane.

The process begins when two ninjurin-1 proteins come together and create a cluster, which then inserts a wedge into the membrane upon receiving the signal for cell death. As more proteins join in, numerous lesions and holes are formed, leading to the gradual cleavage of the cell membrane. This sequential process continues until the cell disintegrates completely, with the body’s own cleaning system responsible for removing the resulting debris.

This groundbreaking study has revealed that ninjurin-1 is indispensable for membrane rupture, dispelling the notion that cells can burst without its involvement. While the influx of ions does cause some swelling, the actual rupture of the membrane relies on the function of this protein. Professor Hiller emphasizes the significance of these structural insights, as they will expand the existing knowledge on cell death found in textbooks.

This newfound understanding of cell death holds immense potential for identifying novel drug targets. It opens up possibilities for therapeutic interventions in cancer treatment, as certain tumor cells evade programmed cell death. Moreover, for conditions characterized by premature cell death, such as neurodegenerative diseases like Parkinson’s, or life-threatening situations like septic shock, drugs that can modulate this process may emerge as viable treatment options.

Source: University of Basel

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