Tanja Maritzen
Leibniz-Institute for Molecular Pharmacology, Germany
Title: AP180 ensures efficient neurotransmission by safeguarding vesicular synaptobrevin/VAMP2 levels
Biography
Biography: Tanja Maritzen
Abstract
Neurotransmission depends on the fusion of neurotransmitter-loaded synaptic vesicles (SVs) with the presynaptic membrane, which is driven by complex formation between the vesicular SNARE Synaptobrevin2 (Syb2) and target SNARE proteins. SV fusion is followed by endocytic SV retrieval and the reformation of SVs of correct size and composition. With 70 copies per SV Syb2 is the most abundant SV protein, yet, 1-3 Syb2 molecules were reported to be sufficient for basal exocytosis. However, we found that a moderate use-dependent reduction of vesicular Syb2 levels caused by absence of its endocytic adaptor AP180 in vivo impairs neurotransmission leading to excitatory/inhibitory imbalance, epileptic seizures, and premature death. Further reduction of Syb2 levels in AP180-/-/Syb2+/- mice results in perinatal lethality, whereas Syb2+/- mice partially phenocopy loss of AP180. Thus, a large vesicular Syb2 pool maintained by AP180 is crucial to sustain efficient neurotransmission.