Subunit-specific and homeostatic regulation of glutamate receptor localization by CaMKII in Drosophila neuromuscular junctions

For the efficient transfer of information across neural circuits, the number of synaptic components at synapses must be appropriately regulated. Here, we found that postsynaptic calcium/calmodulin dependent protein kinase II (CaMKII) modulates the localization of glutamate receptors (GluRs) at Drosophila larval neuromuscular junctions (NMJs). Expression of an inhibitory peptide of CaMKII, Ala, in muscle cells enhanced the density of GluRIIA, which is a major and calcium-permeable subunit of GluR, at synapses of third instar larval NMJs. On the other hand, postsynaptic expression of a constitutively active form of CaMKII (T287D) reduced synaptic GluRIIA. These results suggest that CaMKII regulates GluRIIA at NMJs. Moreover, postsynaptic expression of T287D abolished the accumulation of the scaffolding protein discs large (DLG) at synapses, while exerting no significant effects on the presynaptic area and the localization of cell adhesion molecule fasciclin II (FasII). The amplitude of excitatory junctional potentials (EJPs) was enhanced in Ala-expressing larvae, whereas it was unaffected in T287D-expressing larvae in spite of the prominent loss of GluRIIA. The amplitude of miniature EJPs (mEJPs) was significantly reduced and quantal content was significantly increased in T287D-expressing larvae. Notably, another class of GluR containing GluRIIB was enhanced by the postsynaptic expression of T287D. These results suggest that the homeostatic mechanism in T287D larvae works to maintain the level of synaptic responses. Thus, the Drosophila larval NMJs have several regulatory systems to ensure efficient muscle excitability which is necessary for proper larval movement.