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  RIM-Binding Protein 2 organizes Ca2+channel topography and regulates release probability and vesicle replenishment at a fast central synapse

Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto, R., et al. (2021). RIM-Binding Protein 2 organizes Ca2+channel topography and regulates release probability and vesicle replenishment at a fast central synapse. bioRxiv, 435607. doi:10.1101/2021.03.20.435607.

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Butola, T.1, Author              
Alvanos, T.1, Author              
Hintze, A., Author
Koppensteiner, P., Author
Kleindienst, D., Author
Shigemoto, R., Author
Wichmann, C., Author
Moser, T.1, Author              
Affiliations:
1Research Group of Synaptic Nanophysiology, MPI for Biophysical Chemistry, Max Planck Society, ou_2205655              

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Free keywords: cochlear nucleus, calycealsynapse, short-term plasticity, readily releasable pool, active zone topography, Ca2+influx-exocytosis coupling
 Abstract: RIM-Binding Protein 2 (RIM-BP2) is a multi-domain protein of the presynaptic active zone (AZ). By binding to Rab-interacting protein (RIM), bassoon and voltage-gated Ca²⁺channels (CaV), it is considered to be a central organizer of the topography of CaVand release sites of synaptic vesicles (SVs) at the AZ. Here, we investigated the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers with bushy cells of the cochlear nucleus, a fast relay of the auditory pathway with high release probability. Disruption of RIM-BP2 lowered release probability altering short-term plasticity and reduced evoked excitatory postsynaptic currents (EPSCs). Analysis of SV pool dynamics during high frequency train stimulation indicated a reduction of SVs with high release probability but an overall normal size of the readily releasable SV pool (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion was slowed. Ultrastructural analysis by super-resolution light and electron microscopy revealed an impaired topography of presynaptic CaVand a reduction of docked and membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for establishing a high initial release probability as required to reliably signal sound onset information that we found to be degraded in bushy cells of RIM-BP2-deficient mice in vivo.

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Language(s): eng - English
 Dates: 2021-03-20
 Publication Status: Published online
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 Rev. Type: No review
 Identifiers: DOI: 10.1101/2021.03.20.435607
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Title: bioRxiv
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: 435607 Start / End Page: - Identifier: -