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

Dhananjay A Wagh; Tobias M Rasse; Esther Asan; Alois Hofbauer; Isabell Schwenkert; Heike Dürrbeck; Sigrid Buchner; Marie-Christine Dabauvalle; Manuela Schmidt; Gang Qin; Carolin Wichmann; Robert Kittel; Stephan J Sigrist; Erich Buchner

doi:10.1016/j.neuron.2006.02.008

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

Neuron. 2006 Mar 16;49(6):833-44. doi: 10.1016/j.neuron.2006.02.008.

Authors

Dhananjay A Wagh¹, Tobias M Rasse, Esther Asan, Alois Hofbauer, Isabell Schwenkert, Heike Dürrbeck, Sigrid Buchner, Marie-Christine Dabauvalle, Manuela Schmidt, Gang Qin, Carolin Wichmann, Robert Kittel, Stephan J Sigrist, Erich Buchner

Affiliation

¹ Lehrstuhl für Genetik und Neurobiologie, Theodor-Boveri-Institut für Biowissenschaften, Am Hubland, D-97074 Würzburg, Germany.

PMID: 16543132
DOI: 10.1016/j.neuron.2006.02.008

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / chemistry
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Animals, Genetically Modified
Behavior, Animal
Blotting, Northern / methods
Blotting, Western / methods
Cloning, Molecular
Drosophila
Drosophila Proteins / genetics
Drosophila Proteins / physiology*
Dynamins / metabolism
Electrophoresis, Gel, Two-Dimensional / methods
Green Fluorescent Proteins / biosynthesis
Humans
Immunochemistry / methods
In Situ Hybridization / methods
Intracellular Signaling Peptides and Proteins / chemistry
Intracellular Signaling Peptides and Proteins / metabolism*
Membrane Potentials / drug effects
Membrane Potentials / genetics
Membrane Potentials / physiology
Microscopy, Electron, Transmission / methods
Molecular Sequence Data
Nerve Tissue Proteins / chemistry
Nerve Tissue Proteins / metabolism*
Neuromuscular Junction / physiology*
Neuromuscular Junction / ultrastructure
Presynaptic Terminals / metabolism
RNA Polymerase I
RNA, Messenger / biosynthesis
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction / methods
Structural Homology, Protein*
Walking / physiology

Substances

Adaptor Proteins, Signal Transducing
BRP protein, Drosophila
Drosophila Proteins
ERC1 protein, human
Intracellular Signaling Peptides and Proteins
Nerve Tissue Proteins
RNA, Messenger
RNA, Small Interfering
Green Fluorescent Proteins
POLR1G protein, human
RNA Polymerase I
Dynamins

Associated data

GENBANK/AJ849544