RIM-Binding Protein 2 Organizes Ca2+ Channel Topography and Regulates Release Probability and Vesicle Replenishment at a Fast Central Synapse

2021 | journal article; research paper

Jump to:Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​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. & Wichmann, C.  et al.​ (2021) 
The Journal of Neuroscience41(37) pp. 7742​-7767​.​ DOI: https://doi.org/10.1523/JNEUROSCI.0586-21.2021 

Documents & Media


GRO License GRO License


Butola, Tanvi; Alvanos, Theocharis; Hintze, Anika; Koppensteiner, Peter; Kleindienst, David; Shigemoto, Ryuichi; Wichmann, Carolin ; Moser, Tobias 
Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated Ca2+ channels (CaV), it is considered to be a central organizer of the topography of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2 knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs) with bushy cells (BCs) 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 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 superresolution light and electron microscopy revealed an impaired topography of presynaptic CaV and 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 BCs of RIM-BP2-deficient mice in vivo SIGNIFICANCE STATEMENT Rab-interacting molecule (RIM)-binding proteins (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach to the calyceal endbulb of Held synapse that transmits auditory information at rates of up to hundreds of Hertz with submillisecond precision we demonstrate a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+ influx and abundance of the key priming protein Munc13-1, a reduced rate of SV replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+ channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This hampers transmission of sound onset information likely affecting downstream neural computations such as of sound localization.
Issue Date
The Journal of Neuroscience 
EXC 2067: Multiscale Bioimaging 
SFB 1286: Quantitative Synaptologie 
SFB 1286 | A04: Aktivitätsabhängige morphologische Veränderungen am Endkolben von Held-Synapsen 
SFB 1286 | B05: Quantitative molekulare Physiologie aktiver Zonen in Calyx-Synapsen 
Working Group
RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding) 
RG Wichmann (Molecular Architecture of Synapses) 
External URL



Social Media