FLI Seminar with Dr. Dragomir Milovanovic

Brain functioning critically relies on neuronal communication that mainly occurs by chemical signaling at the specialized contacts known as synapses. At synapses, messenger molecules are packed into synaptic vesicles (SVs), which are secreted upon the arrival of an action potential. Indeed, loss of SVs and synaptic deficits are associated number of neurodegenerative diseases. Hundreds of SVs accumulate at each synaptic bouton. Despite being held together, SVs are highly mobile, so that they can be recruited to the plasma membrane for their rapid release during neuronal activity. However, how such confinement of SVs corroborates with their motility remains unclear. To bridge this gap, we employ ultrafast single-molecule tracking (SMT) in the reconstituted system and in living neurons, demonstrating that SVs can organize into a distinct liquid phase, akin to oil droplets in water.

Our recent work showed that the condensates of synaptic vesicles act as a buffer recruiting disordered synaptic proteins such as alpha-synuclein, a protein implicated in the pathology of Parkinson’s Disease. Recently, the lab discovered that condensates can harbor electric potential at their interfaces, suggesting a new function of condensates as mesoscale capacitors that can store charge. Condensate biology is now emerging as a key mechanism for understanding synapse organization.