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Foundation Young Investigator Gets a New Angle on NF2

By December 14, 2009December 4th, 2023Awareness, NF2-SWN

NF2 researchers have puzzled over how the NF2 gene protein product merlin actually works in the cell. Why does this matter? Because understanding this will help us better figure out how to make drugs that correct merlin function in NF2 tumors and stop them from growing. In a new paper* (abstract) published in Molecular Cell Biology, Children’s Tumor Foundation Young Investigator Awardee Timmy Mani (University of Cincinnati) with a team led by his mentor Dr. Wallace Ip provide a new and unique view of merlin that might advance this area. It has long been known that merlin is related to proteins from the Ezrin Radixin-Moesin (ERM) protein family. ERM proteins are regulated by switching from a ‘closed’ to an ‘open’ conformation, and it has been thought merlin is the same. Mani and colleagues developed a series of probes that allowed them to ‘visualize’ merlin by fluorescence resonance energy transfer (FRET), as purified protein and in living cells. They found something new and unexpected: merlin exists in a stable, closed conformation but when activated undergoes a more subtle change than previously thought. These studies add to a recently growing body of evidence that challenge the standard thinking in the NF2 field. Also, though early stage, this type of research can inform the development of drug therapies aimed at targeting and restoring merlin function, and providing tumor treatments. This work was supported by the NIH, DOD CDMRP and the Children’s Tumor Foundation.