MBExC Lecture

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october, 2022

202211oct3:00 PM4:00 PMMBExC LectureDynamic calcium channel organization within the presynaptic membrane3:00 PM - 4:00 PM MPI-NAT, City Campus, Hermann-Rein-Str. 3Speaker:Prof. Dr. Martin Heine, Johannes Gutenberg University Mainz

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Prof. Dr. Martin Heine from the Institute of Developmental Biology and Neurobiology (iDN), Johannes Gutenberg University Mainz will talk about “Dynamic calcium channel organization within the presynaptic membrane”.

Abstract:

Chemical synapses are essential subcellular structures for information processing and storage within neuronal networks. Their function and structure can change in an activity dependent manner to maintain adequate transmission properties. Key elements to trigger evoked transmitter release are voltage gated calcium channels (VGCC) within the presynaptic membrane. VGCC are tightly linked to the pool of ready releasable vesicles and interact with several scaffold proteins within the active zone (AZ). Despite the well-defined function of VGCC within the process of transmitter release and vesicular recycling the mechanisms how VGCC are recruited, stabilized and maintained within the presynaptic membrane is still unclear. Employing single molecule imaging approaches, we discovered that VGCC show a surprising high dynamic organisation within the presynaptic membrane. Modulating the C-terminal structure of VGCC by expressing different splice variants or altering neuronal activity indicate that the observed dynamic of individual channels adopts in an activity dependent manner. Suggesting that not only channel kinetics but also the arrangement of VGCC within the AZ can contribute within time scales of seconds to minutes to alter presynaptic vesicle release properties.
Taking advantage of the reduced molecular complexity of the Drosophila NMJ we ask the question, to which extend the population of release relevant Cacophony calcium channels is dynamically reorganized during induction and maintenance of presynaptic homeostatic plasticity. Live single particle tracking approaches of endogenous mEOS4b tagged Cacophony channels show a confined but mobile organisation within the AZ of NMJs. The link between the C-terminus of the channel to the N-terminus of the ELKS protein Bruchpilot is necessary for plasticity induction and maintenance. We discovered a robust compaction of VGCC within central nanoclusters of the NMJ, which is essential for the homeostatic modulation of release properties and depend on the abundance of long and short isoforms of Bruchpilot within the synapse. The circadian rhythm dependent regulation of Bruchpilot isoforms in different synapses suggest that the regulation of VGCC dynamics is an important mechanism to maintain presynaptic plasticity.

Host: Prof. Dr. Tina Pangršič

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