Retrograde Control of Synaptic Transmission by Postsynaptic CaMKII at the Drosophila Neuromuscular Junction

• Published in: Neuron (Cambridge, Mass.) Vol. 39; no. 2; pp. 255 - 267
• Main Authors: Haghighi, A.Pejmun, McCabe, Brian D., Fetter, Richard D., Palmer, Jessica E., Hom, Sabrina, Goodman, Corey S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.07.2003; Elsevier Limited
• Subjects: Animals; Animals, Genetically Modified; Calcium - pharmacology; Calcium-Binding Proteins; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium-Calmodulin-Dependent Protein Kinases - physiology; Dose-Response Relationship, Drug; Drosophila melanogaster; Electrophysiology; Excitatory Postsynaptic Potentials - genetics; Excitatory Postsynaptic Potentials - physiology; Failure analysis; Gene Expression Regulation, Enzymologic; Genes, Insect; Homeostasis; Immunohistochemistry; Insects; Kinases; Mannosyltransferases - metabolism; Mannosyltransferases - physiology; Membrane Glycoproteins - metabolism; Microscopy; Microscopy, Electron; Muscles - metabolism; Muscles - physiology; Mutagenesis; Nerve Tissue Proteins - metabolism; Neuromuscular Junction - enzymology; Neuromuscular Junction - physiology; Neuromuscular Junction - ultrastructure; Neurons - metabolism; Neurons - physiology; Neurotransmitter Agents; Peptide Fragments - physiology; Presynaptic Terminals - enzymology; Presynaptic Terminals - ultrastructure; Quantum Theory; Receptors, AMPA - genetics; Receptors, AMPA - physiology; Rodents; Saccharomyces cerevisiae Proteins; Software; Synaptic Transmission - physiology; Synaptotagmins
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(03)00427-6

Retrograde signaling plays an important role in synaptic homeostasis, growth, and plasticity. A retrograde signal at the neuromuscular junction (NMJ) of Drosophila controls the homeostasis of neurotransmitter release. Here, we show that this retrograde signal is regulated by the postsynaptic activity of Ca 2+/calmodulin-dependent protein kinase II (CaMKII). Reducing CaMKII activity in muscles enhances the signal and increases neurotransmitter release, while constitutive activation of CaMKII in muscles inhibits the signal and decreases neurotransmitter release. Postsynaptic inhibition of CaMKII increases the number of presynaptic, vesicle-associated T bars at the active zones. Consistently, we show that glutamate receptor mutants also have a higher number of T bars; this increase is suppressed by postsynaptic activation of CaMKII. Furthermore, we demonstrate that presynaptic BMP receptor wishful thinking is required for the retrograde signal to function. Our results indicate that CaMKII plays a key role in the retrograde control of homeostasis of synaptic transmission at the NMJ of Drosophila.