Research Topic
In this CRC project we focus on the formation and dynamics of the endocytic signaling platform and its coupling to the exocytosis domains at synapses. We will analyze whether synaptic vesicle proteins and lipids remain in part clustered after exocytosis, we will determine the required factors, and determine the mechanisms underlying the tight coupling of exocytosis and compensatory endocytosis.
Maintaining synaptic transmission requires resorting and retrieval of the fused vesicle components by compensatory endocytosis. We showed in previous studies the existence of a pre-sorted and pre-assembled readily retrievable pool (RRetP) of synaptic vesicle proteins, and identified one of them, synaptophysin 1, to be a main organizer of the RRetP by forming hetero-oligomers with the v-SNARE synaptobrevin. However, are self-assembly forces of SV components sufficient for re-clustering or do endocytic adaptor proteins and clathrin contribute? To address these questions, we utilize fluorescence live-cell imaging as well as nanoscopy and correlative electron microscopy. We also developed a novel synaptic culture system, “Xenapses”, amenable to live-cell total internal reflection microscopy. Xenapses are synapses formed by cultured mouse hippocampal neurons on micropatterned host substrates functionalized with synaptogenic proteins. Xenapses show all the hallmarks of a typical synapse, both structurally and physiologically.
Selected Publications
- Duan, J., Kahms, M., Steinhoff, A., Klingauf, J. (2024) Spontaneous and evoked synaptic vesicle release arises from a single releasable pool. Cell Reports, 43: 7114461. doi.org/10.1016/j.celrep.2024.114461.
- Schnieder, M., Niemann, A., Hüve, J., Klingauf, J. (2024). Collimating three-axicon zoom system for interferometric Bessel beam side lobe cancellation. Opt Quant Electron, 56: 716. doi.org/10.1007/s11082-023-06229-y.
- Krishnan, S., Klingauf, J. (2023). The readily retrievable pool of synaptic vesicles. Biological Chemistry, 404(5): 385-397. doi.org/10.1515/hsz-2022-0298.
- Mancinelli, G., Lamparter, L., Nosov, G., Saha, T., Pawluchin, A., Kurre, R., Rasch, C., Ebrahimkutty, M., Klingauf, J., Galic, M. (2021). Dendrite tapering actuates a self-organizing signaling circuit for stochastic filopodia initiation in neurons. Proc Natl Acad Sci USA, 118(43)::e2106921118. doi.org/10.1073/pnas.2106921118.
- Goossen-Schmidt, N.C., Schnieder, M., Hüve, J., Klingauf, J. (2020). Switching behaviour of dSTORM dyes in glycerol-containing buffer. Sci Rep. 10(1): 13746. doi.org/10.1038/s41598-020-70335-0.