A new study sheds light on how a molecule recognizes the certain type of tumor and disarms the harmful protein causing a tumor.
Notch Signaling Pathway
Notch signaling pathway is present in the most multicellular organism and is very important for embryonic development. This type of cell signaling pathway helps in maintaining a balance of stem cell in brain and body.
If Notch signaling is activated irregularly in neural progenitor cells whose function is to send a signal to neural stem cells, it can lead to overproduction of these stem cell in the brain which in turn can cause the development of brain.
“However, the molecular mechanisms that prevent abnormal Notch signaling activation and potentially harmful decisions related to cell fate remain unclear.”
To address this question, researchers carried out genetic and biochemical tests to study stem cells called neuroblasts in the central brain region of fruit fly larvae. They specifically analyzed the retromer protein complex. The function of this protein complex is to transport the specific cargo proteins from endosomes to the cell surface. Endosomes are a type of membrane-bound compartment inside cells.
Finding of the study
Their study led to to the finding that the function of the retromer complex is to regulate Notch protein trafficking in neural progenitors. Notch receptors are activated incorrectly if the retromer complex is inactive. This lead multiplication of neural stem cells excessively and increasing the risk of brain tumor formation.
“We found that a sufficient amount of Notch protein needs to be destroyed in neural progenitors to maintain the one-way Notch signaling pathway between these progenitors and neural stem cells,” explains co-first author Chouin Wong, Graduate Student at Peking University.
“When an excess of Notch protein fails to be destroyed in neural progenitors, this is normally recognized by the retromer complex and is rapidly transported away from the endosomes inside cells. But when the retromer complex is inactive, this pool of Notch protein increases massively in the endosomes and is ‘ignited’ abnormally.”
The Bomb Squad
With this study in mind, researchers suggest that retromer complex serves as a ‘bomb squad’ which identify and disarm the irregularly activated Notch receptors in a timely manner, thereby preventing the risk of brain tumors forming in this way.
“In light of these findings, we believe further investigation into the regulatory mechanisms underlying Notch overactivation is necessary,” concludes senior author Yan Song, Principal Investigator at Peking University. “In particular, a deeper understanding of how to prevent abnormal Notch signaling activation in neural progenitors could potentially provide a new approach for treating brain tumors in future.”