Abstract
Synaptic growth at the Drosophila melanogaster neuromuscular junction (NMJ) depends on the endocytosis and downstream intracellular trafficking of signaling receptors. Nervous wreck (Nwk) is an F-BAR/SH3 protein that regulates trafficking of the signaling receptors in motor neuron terminals to attenuate neuronal growth. Little is known about how Nwk’s trafficking activity is regulated in vivo to achieve precise signal-specific activity. Here I show that Nwk is autoinhibited by an intramolecular interaction between its F-BAR domain and its SH3b domain. I show that the SH3b ligand Dynamin-associating protein 160 kD (Dap160) does not relieve this autoinhibition in cell culture. I also show that the SH3b domain of Nwk, though required, is not sufficient for interaction with Dap160 and that Dap160 has an affinity for the F-BAR domain of Nwk. I propose that the tertiary folding of Nwk reveals the binding sequence for Dap160. In the future, I will further investigate the mechanisms of intra- and intermolecular regulation of Nwk in order to better understand how Nwk controls healthy neuronal development.