The Abl-Interactor Abl Regulates Synaptic Development and Neuronal Survival via Inhibition of BMP Sinaling

Objectives: Abl tyrosine kinase regulates multiple aspects of neuronal morphogenesis by modulating actin dynamins. Abi (Abl interactor), a substrate of the Abl kinase, also plays an essential role in Scar/Wave complex-mediated actin regulation; however, its role in the nervous system is still pooly defined. Here we show that Drosophila Abi is an important regulator of synaptic development and neuronal survival.
Methods: We use Drsophila NMJ as a model system to study the role of Abi and Abl in synapse.
Results: Abi is highly enriched at neuromuscular junction (NMJ) synapses. Loss of Abi causes synaptic overgrowth at the NMJ and increases bone morphogenetic protein (BMP) signaling in motor neurons. Transgenic rescue experiments suggest that the Abl-, Scar-, and Kette-binding activities of Abi, as well as its phosphorylation by Abl, are required presynaptically for normal synaptic growth. A synaptic overgrowth phenotype is also induced by presynaptic depletion of Abl or components of the Scar/Wave complex. Genetic interaction experiments suggest that Abi restrains synaptic growth by negatively regulating BMP signaling. Finally, depletion of neu¬ronal Abi or neuronal overexpression of dominant negative Abl causes brain neurodegeneration, which is also induced by elevated BMP signaling.
Conclusions: We propose that the regulation of the Scar/Wave complex by Abl/Abi is essential for BMP-dependent synaptic growth and neuronal survival. We are currently investigating the mechanism by which the Abl-Abi-Scar pathway regulates BMP signaling in motor neurons.