Vesicular Transporters; Mechanisms of Dense-Core Vesicle and Synaptic Vesicle Release

Neurons communicated by translating an electrical signal into the release of neurotransmitter. Classical neurotransmitters, such as glutamate, GABA, and glycine are loaded into synaptic vesicles (SVs) by vesicular transporters and released at synaptic contact sites to either activate or inhibit the postsynaptic cell. The balance between excitation and inhibition is essential for brain function, and imbalances play a role in neurological disorders as divergent as epilepsy and schizophrenia. In addition to the classical neurotransmitters, many neurons produce bioactive compounds such as growth factors and neuropeptides, which are packaged in dense-core vesicles (DCVs), and whose release and mode of action are less tightly restricted in space and time than those of classical neurotransmitters. They nonetheless profoundly influence numerous aspects of our physiology, from neuronal excitability to gene expression, and are equally essential for normal brain function.

We are using genetic mouse models, cell biology, and electrophysiology to investigate the fundamental mechanisms of SV and DCV release in neurons and in neuroendocrine chromaffin cells. Unlike neuronal DCVs, chromaffin cell DCVs contain adrenaline and noradrenaline, and fusion of DCVs with the cell membrane as well as DCV content release can easily be monitored in this cell type. In addition to analyzing and comparing the molecular processes that control SV and DCV exocytosis, we are also studying the cellular functions of vesicular transporters, which aside from their main task of filling vesicles, affect other cell biological processes, such as vesicle recycling.