In a report that is the cover article in the current issue of the journal Cell, Dr. Hugo Bellen, BCM professor of molecular and human genetics and a Howard Hughes Medical Institute investigator, and his colleague Dr. P. Robin Hiesinger demonstrate that a protein called Vha100-1, a member of the pore-forming V0 complex, plays a crucial role in the transmission of a message from one nerve cell to another.
The fusion of vesicles that connect the neurotransmitter to the membrane of the cell is a critical step in this transfer. Whether neurotransmitter is released through a protein pore has been a matter of debate for many years. Previously, it was believed that SNARE (soluble N-ethylmaleimidesensitive factor attachment protein receptor) proteins were all that was needed for this fusion.
In this paper, Bellen and his colleagues argue that Vha100-1 is another component that together with the SNARES are critical for the fusion and the release of a neurotransmitter. They identified this protein through a special screening procedure in fruit flies that allows them to identify functional defects in the fly eye.
They found that the mutant fly eyes that lacked Vha100-1 were blind, indicating that information was not being communicated, said Bellen. Using molecular genetics, electrophysiology, biochemistry, electron microscopy and yeast trans-species experiments, they determined that Vha100-1 was involved in membrane fusion and played a critical role in the release of a neurotransmitter after the action of the SNARE proteins.
Others who participated in the research include Drs. Amir Fayyazuddin, Sunil Q. Mehta, Tanja Rosenmund, Karen L. Schulze, Patrik Verstreken, Yu Cao, Yi Zhou and Jeannette Kunz.
Cell