Researchers at the University of Haifa have found that the Notch receptor not only receives signals from other cells, but also activates neighboring cells and signals them to engulf living cells. The finding may change the understanding of Notch-related diseases, including cancers.
In a new study conducted at the University of Haifa, and published in the journal Nature Communications., it has been found that a central mechanism in communication between cells works differently than previously thought. The finding may explain why treatments for serious diseases, including cancer, have not led to notable results so far. At the center of the study is the Notch receptor, a central protein in communication between cells, which has already been linked in the past to various diseases, including types of cancer. Contrary to the conventional understanding that Notch acts only as a receptor for signals from other cells, the researchers showed that the receptor is also capable of acting as a signal, which activates neighboring cells and even signals them to ingest living cells. This is a fundamental change in the scientific perception of Notch activity. "It is possible that the new mechanism we found could provide an explanation for why treatments that focused only on activity within the cell have not led to notable results so far, since the Notch receptor also acts as a signal to neighboring cells and affects neighboring cells," said Prof. Hila Toledano of the University of Haifa, one of the study's authors.
Intercellular communication
Intercellular communication is a central biological process that allows cells to transmit information to each other and coordinate complex activity in tissues and organs. In this process, cells "transmit" molecular signals that are received by other cells through specialized receptors located on the surface of the cell membrane. When such a signal binds to the receptor, it causes a change in the activity of the receiving cell, thereby affecting its function, condition, and even fate. This mechanism is essential for the precise regulation of processes such as embryonic development, cell differentiation, and maintaining proper balance in tissues. One of the central receptors in this communication is the Notch receptor, which was discovered over a century ago in fruit flies. Disruptions in this pathway in humans have been linked to a wide range of diseases, including cancers, Aljell syndrome, and CADASIL disease. Against this background, doctoral students Heba Abu Rumi and Nivin Sarhan, research students in the laboratory of Prof. Hila Toledano from the Department of Human Biology at the University of Haifa, sought to examine whether the Notch receptor acts solely as a receptor that receives signals from other cells, or whether it plays an additional role in communication between cells.
The researchers used a fruit fly research model, which allows for the tracking of cellular processes with high precision. They combined advanced live imaging methods, fluorescent staining to identify live and dead cells, and genetic manipulations that allowed them to increase or decrease the expression levels of the Notch receptor in cells. They also compared different versions of the protein, including ones that lack the internal part responsible for classical signaling, and examined how these changes affect cell behavior.
Immune system cells engulf cancer cells
The results of the study indicate that the Notch receptor does not only act as a signal receptor, but also as a signal that activates neighboring cells. It was found that Notch binds directly to a receptor called Draper in neighboring cells, thus activating a process in which these cells engulf living cells, in a process known as 'phagoptosis.' Surprisingly, the process does not depend on the intrinsic signaling activity of Notch, but occurs even when this part of the protein is inactive. This shows that its activity as a signal to neighboring cells is independent of the known signaling mechanism of Notch. The study also found that increasing Notch levels in cells led to a significant increase in cell death, while reducing it reduced the process, and that without the Draper receptor, the process does not occur at all. These findings indicate a fundamental change in the understanding of the direction of signaling between cells. "The findings suggest a paradigm shift in intercellular communication and the interpretation of Notch-related diseases. If this mechanism also exists in diseases caused by Notch mutations, it is possible that treatments that focus only on its activity within the cell are ineffective and the direction of signaling and the receptors involved in the disease should be reexamined," the researchers concluded.
More of the topic in Hayadan:
One response
proofreading suggestions:
"The Notch receptor (in) cells. Also,"
"Without the Draper receptor (the) procedure"
Who does Notch signal to ingest? The signaling cell, or just another cell?