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Emerging evidence in both vertebrates and invertebrates is redefining Neuroligins(Nlgs)as active and mobile players in synapse formation,maturation,and function.However,the molecular mechanisms through which neuroligin and other proteins interact with each other to regulate these processes is not well known.Neuroligins are neuronal cell adhesion molecules implicated in synaptic development and function.Although mutations in Nlgs affect postsynaptic differentiation,the molecular mechanism is not clear. In the present thesis,we use Drosophila melanogaster,a simple and genetically tractable model system,to understand the molecular mechanisms and role of Nlg2in cytoskeleton growth at neuromuscular junctions(NMJs).We show that DNlg2is required for postsynaptic cytoskeleton growth.dnlg2mutant exhibit reduced F-actin andα-Spectrin levels at neuromuscular junctions(NMJs).Using GST-pull down and mass spectrometry,we find that DNlg2interacts with Annexin B9(AnxB9),α-Spectrin and actin binding protein.AnxB9localization is impaired in the dnlg2mutant,and the F-actin andα-Spectrin defects can be rescued by genetic overexpression of AnxB9.Furthermore,immunostaining results show reduced bouton numbers and GluRIIB level in AnxB9knockdown flies.AnxB9perturbation cause sever synapse loss and impairment of cytoskeleton organization. Our results reveal a previously unknown role of DNlg2-AnxB9interaction in the regulation of postsynaptic actin cytoskeleton and provide new mechanistic insights into the role of DNlg2in postsynaptic development.The interaction between Dnlg2and AnxB9is also required for NMJ development.