Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila
Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila
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.
- European Neuroscience Institute Göttingen Germany
- University of Göttingen Germany
- Eni (Italy) Italy
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
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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