Regulation of neuromuscular synapse development by Hts in Drosophila

Hu-Li-Tai-Shao (Hts) is a multifunctional protein expressed in the Drosophila nervous system. However, it is unclear whether Hts is involved in controlling synapse structure and function. In this study, I examined the distribution of Hts in Drosophila larvae and found that Hts presents at neuromuscular junctions (NMJs) and partially colocalizes with Discs-large (Dlg). We found that Hts is involved in axonal branching and synapse formation during embryogenesis. Hts loss-of-function decreased NMJ complexity, while Hts gain-of-function increased NMJ complexity. Investigations of mechanisms of Hts in regulating synapse development showed that Hts interacts with Dlg in vivo and phosphomimic-Hts led to an increase in NMJ complexity. My data suggests that phosphorylation of serine705 in the MARCKS domain mediated Hts effects on NMJ structure and plasticity. These results indicate that effects of Hts on NMJ development are likely mediated by protein-protein interactions between Hts, Dlg and other proteins and are regulated by phosphorylation/dephosphorylation cycles.