Terminal axonal arborization and synaptic bouton formation critically rely on abp1 and the arp2/3 complex.
Neuronal network formation depends on properly timed and localized generation of presynaptic as well as postsynaptic structures. Although of utmost importance for understanding development and plasticity of the nervous system and neurodegenerative diseases, the molecular mechanisms that ensure the fine-control needed for coordinated establishment of pre- and postsynapses are still largely unknown. We show that the F-actin-binding protein Abp1 is prominently expressed in the Drosophila nervous system and reveal that Abp1 is an important regulator in shaping glutamatergic neuromuscular junctions (NMJs) of flies. STED microscopy shows that Abp1 accumulations can be found in close proximity of synaptic vesicles and at the cell cortex in nerve terminals. Abp1 knock-out larvae have locomotion defects and underdeveloped NMJs that are characterized by a reduced number of both type Ib synaptic boutons and branches of motornerve terminals. Abp1 is able to indirectly trigger Arp2/3 complex-mediated actin nucleation and interacts with both WASP and Scar. Consistently, Arp2 and Arp3 loss-of-function also resulted in impairments of bouton formation and arborization at NMJs, i.e. fully phenocopied abp1 knock-out. Interestingly, neuron- and muscle-specific rescue experiments revealed that synaptic bouton formation critically depends on presynaptic Abp1, whereas the NMJ branching defects can be compensated for by restoring Abp1 functions at either side. In line with this presynaptic importance of Abp1, also presynaptic Arp2 and Arp3 are crucial for the formation of type Ib synaptic boutons. Interestingly, presynaptic Abp1 functions in NMJ formation were fully dependent on the Arp2/3 complex, as revealed by suppression of Abp1-induced synaptic bouton formation and branching of axon terminals upon presynaptic Arp2 RNAi. These data reveal that Abp1 and Arp2/3 complex-mediated actin cytoskeletal dynamics drive both synaptic bouton formation and NMJ branching. Our data furthermore shed light on an intense bidirectional functional crosstalk between pre- and postsynapses during the development of synaptic contacts.
Institute for Biochemistry I, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany; Research Group Membrane Trafficking and Cytoskeleton, Department of Neurochemistry & Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Nicole
N
Koch
Research Group Functional Genetics of the Synapse, Department of Neurochemistry & Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Oliver
O
Kobler
Research Group Functional Genetics of the Synapse, Department of Neurochemistry & Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Ulrich
U
Thomas
Institute for Biochemistry I, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
Britta
B
Qualmann
Institute for Biochemistry I, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany; Research Group Membrane Trafficking and Cytoskeleton, Department of Neurochemistry & Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
Michael M
MM
Kessels
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development*; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009415:Nerve Net / Q000254:growth & development*; D009469:Neuromuscular Junction / Q000254:growth & development*; D017729:Presynaptic Terminals / Q000502:physiology*
C000594255:Abp1 protein, Drosophila; D051376:Actin-Related Protein 2-3 Complex; D029721:Drosophila Proteins; D008840:Microfilament Proteins