Retrograde control of synaptic transmission by postsynaptic CaMKII at the Drosophila neuromuscular junction.
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 Ca2+/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.
Haghighi
A Pejmun
AP
Life Sciences Addition, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. pejmunh@socrates.berkeley.edu
McCabe
Brian D
BD
Fetter
Richard D
RD
Palmer
Jessica E
JE
Hom
Sabrina
S
Goodman
Corey S
CS
D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D017344:Genes, Insect; D007150:Immunohistochemistry; D008364:Mannosyltransferases / Q000378:metabolism / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D009132:Muscles / Q000378:metabolism / Q000502:physiology; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents; D010446:Peptide Fragments / Q000502:physiology; D017729:Presynaptic Terminals / Q000201:enzymology / Q000648:ultrastructure; D011789:Quantum Theory; D018091:Receptors, AMPA / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D009435:Synaptic Transmission / Q000502:physiology*; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D018091:Receptors, AMPA; D029701:Saccharomyces cerevisiae Proteins; D050857:Synaptotagmins; C068701:KRE2 protein, S cerevisiae; D008364:Mannosyltransferases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium