The main goal of CellCellEM is to delineate cellular communication through understanding signaling at the structural and at the molecular levels. The project was designed to primarily characterize the structure and function of individual signaling proteins residing at the cellular membrane, but also to understand the way they communicate with their partners within the cell, outside the cell, and inside the cellular membrane. Specifically, the project focused on GPCRs, that are highly abundant in the CNS and are known to maintain multifaced interactions with proteins and small molecules within the cell, the cellular membrane and in neighboring cells. However, the initial scope of the project expanded way beyond and also covered the exploration of the evolutionary evolvement of signaling. This, yet ongoing work in our group lead to the discovery of a novel family of proteins, the bestrhodopsins, that are light activated ion channels composed of rhodopsins (GPCR ancestors) fused to bestrophin ion channels. A paper describing the bestrhodopsin discovery was published by our group (Rozenberg et al. Nature Struct. Mol. Biol. 2022). The study on bestrhodopsins is currently ongoing in the lab and as rhodopsins are considered to be ancestors of GPCRs, these studies may potentially provide hints regarding the evolution of signaling mechanisms and aid in understanding the inner workings of the more complex signaling pathways in our brain. Altogether these studies are an evolvement of the suggested ERC project and were conducted in parallel to our work on the explicit aims presented in the original proposal.
