Title: Molecular Mechanism of Synaptic Vesicle Exo-Endocytosis
Abstract: Fast neurotransmission is crucial for brain function and depends on the exo-endocytic cycling of synaptic vesicles (SVs). Malfunction or loss of select SV proteins is associated with impaired viability, defective neurotransmitter release and with neurodegeneration. In my talk I will focus on two aspects of this process: First, I will describe our recent studies regarding the mechanism by which fast exocytic vesicle fusion at active zones is coupled to the endocytic retrieval of SV membranes. Second, I will discuss the pathways by which SV proteins are sorted and regenerated through multiple rounds of SV cycling at synapses. We have recently identified molecular scaffolds that may link SV exocytosis and endocytosis as well as endocytic adaptors for the specific sorting of select SV membrane proteins. References: 1. von Kleist, L., et al. & Haucke, V. Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell 146, 471-484 (2011). 2. Haucke, V., Neher, E. & Sigrist, S.J. Protein scaffolds in the coupling of synaptic exocytosis and endocytosis. Nat Rev Neurosci. 12, 125-136 (2011). 3. Koo, S.Y., Markovic, S., Puchkov, D., Mahrenholz, C., Beceren-Braun, F., Maritzen, T., Dernedde, J., Volkmer, R., Oschkinat, O., Haucke, V. (2011) SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors CALM and AP180 at synapses. Proc. Natl. Acad. Sci. USA, 108, 13540-13545. 4. Faelber, K., Posor, Y., Gao, S., Held, M., Roske, Y., Schulze, D., Haucke, V., Noe, F., Daumke, O. (2011) Crystal structure of nucleotide-free dynamin. Nature, 477, 556-560. 5. Diril, M. K., Wienisch, M., Jung, N., Klingauf, J., and Haucke, V. (2006) Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization. Dev. Cell 10, 233-244.