The assembly of SNARE proteins that reside in the synaptic vesicle and presynaptic plasma membranes provides the energy to drive neurotransmitter release. This process underlies information flow in the central nervous system, and mutations in the SNAREs are linked to significant mental disorders such as Schizophrenia. In spite of its importance, the steps and molecular structures leading to SNARE assembly and the mechanisms by which calcium triggers the release of neurotransmitter from neurons have not been clarified. The mechanisms by which the calcium sensor, synaptotagmin 1, drives fusion is not known and highly debated, and the state of the SNARE proteins and their associated regulatory proteins prior to fusion are not known.
We have an ongoing collaborative interdisciplinary effort with Lukas Tamm (Molecular Physiology, Univ. of VA) and Reinhard Jahn (MaxPlank Institute for Biophysical Chemistry, Gottingen Germany) to elucidate the precise molecular mechanisms that drive exocytosis and the controlled release of neurotransmitter at the nerve terminus. This work is currently funded by a program project grant from the Institute of General Medical Sciences at the NIH.