title: Presynaptic CamKII regulates activity-dependent axon terminal growth.
abstract: Spaced synaptic depolarization induces rapid axon terminal growth and the formation of new synaptic boutons at the Drosophila larval neuromuscular junction (NMJ). Here, we identify a novel presynaptic function for the Calcium/Calmodulin-dependent Kinase II (CamKII) protein in the control of activity-dependent synaptic growth. Consistent with this function, we find that both total and phosphorylated CamKII (p-CamKII) are enriched in axon terminals. Interestingly, p-CamKII appears to be enriched at the presynaptic axon terminal membrane. Moreover, levels of total CamKII protein within presynaptic boutons globally increase within one hour following stimulation. These effects correlate with the activity-dependent formation of new presynaptic boutons. The increase in presynaptic CamKII levels is inhibited by treatment with cyclohexamide suggesting a protein-synthesis dependent mechanism. We have previously found that acute spaced stimulation rapidly downregulates levels of neuronal microRNAs (miRNAs) that are required for the control of activity-dependent axon terminal growth at this synapse. The rapid activity-dependent accumulation of CamKII protein within axon terminals is inhibited by overexpression of activity-regulated miR-289 in motor neurons. Experiments in vitro using a CamKII translational reporter show that miR-289 can directly repress the translation of CamKII via a sequence motif found within the CamKII 3' untranslated region (UTR). Collectively, our studies support the idea that presynaptic CamKII acts downstream of synaptic stimulation and the miRNA pathway to control rapid activity-dependent changes in synapse structure.
authors: Department of Biological Sciences, Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.
authors: Katherine R
authors: KR
authors: Nesler
authors: Department of Biological Sciences, Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.
authors: Emily L
authors: EL
authors: Starke
authors: Department of Biological Sciences, Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.
authors: Nathan G
authors: NG
authors: Boin
authors: Department of Biological Sciences, Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA.
authors: Matthew
authors: M
authors: Ritz
authors: Department of Biological Sciences, Eleanor Roosevelt Institute, University of Denver, Denver, CO 80210, USA; Molecular and Cellular Biophysics Program, University of Denver, Denver, CO 80210, USA. Electronic address: scott.barbee@du.edu.
authors: Scott A
authors: SA
authors: Barbee
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004330:Drosophila; D008564:Membrane Potentials; D035683:MicroRNAs / Q000235:genetics; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology; D000071446:Neuronal Outgrowth; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; C586148:MIRN289 microRNA, Drosophila; D035683:MicroRNAs; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Activity-dependent axon terminal growth; CamKII; NMJ; miRNA pathway