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Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila

Authors: Wagh, Dhananjay A.; Rasse, Tobias M.; Asan, Esther; Hofbauer, Alois; Schwenkert, Isabell; Dürrbeck, Heike; Buchner, Sigrid; +7 Authors

Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila

Abstract

Neurotransmitters are released at presynaptic active zones (AZs). In the fly Drosophila, monoclonal antibody (MAB) nc82 specifically labels AZs. We employ nc82 to identify Bruchpilot protein (BRP) as a previously unknown AZ component. BRP shows homology to human AZ protein ELKS/CAST/ERC, which binds RIM1 in a complex with Bassoon and Munc13-1. The C terminus of BRP displays structural similarities to multifunctional cytoskeletal proteins. During development, transcription of the bruchpilot locus (brp) coincides with neuronal differentiation. Panneural reduction of BRP expression by RNAi constructs permits a first functional characterization of this large AZ protein: larvae show reduced evoked but normal spontaneous transmission at neuromuscular junctions. In adults, we observe loss of T bars at active zones, absence of synaptic components in electroretinogram, locomotor inactivity, and unstable flight (hence "bruchpilot"-crash pilot). We propose that BRP is critical for intact AZ structure and normal-evoked neurotransmitter release at chemical synapses of Drosophila.

Keywords

Dynamins, Behavior, Animal, PROTEINS, Neuroscience(all), Immunochemistry, Blotting, Western, Green Fluorescent Proteins, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Nerve Tissue Proteins, Blotting, Northern, MOLNEURO, Membrane Potentials, Animals, Genetically Modified, Microscopy, Electron, Transmission, Animals, Drosophila Proteins, Humans, CELLBIO, Drosophila, Electrophoresis, Gel, Two-Dimensional, Cloning, Molecular, In Situ Hybridization, Adaptor Proteins, Signal Transducing

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
828
Top 0.1%
Top 1%
Top 0.1%
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