Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila

Wagh, Dhananjay A. and Rasse, Tobias M. and Asan, Esther and Hofbauer, Alois and Schwenkert, Isabell and Durrbeck, Heike and Buchner, Sigrid and Dabauvalle, Marie-Christine and Schmidt, Manuela and Olin, Gang and Wichmann, Carolin and Kittel, Robert and Sigrist, Stephan J. and Buchner, Erich (2006) Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila. NEURON, 49 (6). pp. 833-844. ISSN 0896-6273, 1097-4199

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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.

Item Type: Article
Uncontrolled Keywords: RIM-BINDING PROTEINS; GLUTAMATE-RECEPTOR; NEUROMUSCULAR-JUNCTIONS; NEUROTRANSMITTER RELEASE; PRESYNAPTIC CYTOMATRIX; MUTANT DROSOPHILA; WILD-TYPE; ULTRASTRUCTURE; MELANOGASTER; CAST;
Subjects: 500 Science > 590 Zoological sciences
Divisions: Biology, Preclinical Medicine > Institut für Zoologie > Entwicklungsbiologie (Prof. Dr. Stephan Schneuwly)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 17 Feb 2021 12:42
Last Modified: 17 Feb 2021 12:42
URI: https://pred.uni-regensburg.de/id/eprint/34785

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