The secretion of neurotransmitters and hormones is essential for brain function and neuroendocrine signalling. A common hallmark in all neuroendocrine systems is the assembly of a SNARE complex. SNARE assembly is tightly controlled by accessory proteins that couple secretory events to a stimulus and modulate secretory strength.

The fastest known type of secretion is used by synapses in the brain. After the arrival of an action potential in the synapse, the entry of Ca²⁺ ions is coupled within milliseconds to a secretory event. This coupling involves synaptotagmin-1, a vesicle-associated protein that contains binding sites for Ca²⁺, phospholipids as well as the SNARE complex.

While fast neurotransmission in the brain is essential for life, it is becoming increasingly clear that slower modes of secretion also contribute to overall brain function. An example is found in DOC2 proteins, cytoplasmic C2 domain proteins with a very high Ca²⁺ affinity. They reversibly associate with the plasma membrane in an activity-dependent manner to enhance SNARE-driven exocytosis. This mode of activation provides a means to trigger secretory events in reponse non-classical Ca²⁺ signals, as opposed to classical transients induced by action potentials.

My research focuses on molecular mechanisms of regulated exocytosis. In addition to C2 domain proteins like DOC2, PCLO and rabphilin, I am also interested in the role of tomosyn-like proteins that appear to inhibit the secretion of plasmalemmal or neurotransmitter-containing vesicles at non-supported sites. Studies in tomosyn-deficient mice should provide more insight in the biological relevance of this mechanism in the mammalian brain.