Michael Sars Centre

Prof. Thomas Söllner, Heidelberg University Biochemistry Center (BZH), Germany

Research Group Leader Thomas Söllner from Heidelberg University Biochemistry Center (BZH) will present: "Molecular machinery and mechanisms mediating and controlling neurotransmitter release".

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Thomas Söllner

Neurotransmitter release is orchestrated by a cascade of reactions and components, conferring spatially and temporally controlled synaptic vesicle fusion. The reaction pathway starts with the tethering of synaptic vesicles to the active zone at the nerve terminal, followed by vesicle priming, generating a readily releasable vesicle pool and finally culminates in Ca2+-triggered fusion pore opening on a submillisecond time scale. Locally restricted vesicle tethering involves Rab3 on synaptic vesicles and its interacting partner Rim1 at the active zone. Munc13-1 and Munc18-1 control the subsequent assembly of the fusion machinery – the v-SNARE VAMP2 on synaptic vesicles and the t-SNAREs syntaxin1 and SNAP-25 on the plasma membrane – into a partially assembled metastable four helical bundle. Further zippering of the four-helix bundle is constrained by the Ca2+ sensor Synaptotagmin1 on synaptic vesicles and the cytosolic protein complexin and accelerated by the local increase of Ca2+. In addition, lipids such as diacylglycerol and PI(4,5)P2 play key roles as interacting partners at several steps, likely contributing to local membrane bridging, shaping, lipid segregation and merger. We are using purified components and reconstituted vesicle docking/fusion assays to decipher distinct steps at their mechanistic and structural levels. Our goal is to establish a fully reconstituted system to understand the exact interplay of all components during the entire reaction cascade and their regulation by physiological signals.

Visit Prof. Söllner's website.