title: Cortactin Is a Regulator of Activity-Dependent Synaptic Plasticity Controlled by Wingless.
abstract: Major signaling molecules initially characterized as key early developmental regulators are also essential for the plasticity of the nervous system. Previously, the Wingless (Wg)/Wnt pathway was shown to underlie the structural and electrophysiological changes during activity-dependent synaptic plasticity at theDrosophilaneuromuscular junction. A challenge remains to understand how this signal mediates the cellular changes underlying this plasticity. Here, we focus on the actin regulator Cortactin, a major organizer of protrusion, membrane mobility, and invasiveness, and define its new role in synaptic plasticity. We show that Cortactin is present presynaptically and postsynaptically at theDrosophilaNMJ and that it is a presynaptic regulator of rapid activity-dependent modifications in synaptic structure. Furthermore, animals lacking presynaptic Cortactin show a decrease in spontaneous release frequency, and presynaptic Cortactin is necessary for the rapid potentiation of spontaneous release frequency that takes place during activity-dependent plasticity. Most interestingly, Cortactin levels increase at stimulated synaptic terminals and this increase requires neuronal activity,de novotranscription and depends on Wg/Wnt expression. Because it is not simply the presence of Cortactin in the presynaptic terminal but its increase that is necessary for the full range of activity-dependent plasticity, we conclude that it probably plays a direct and important role in the regulation of this process.SIGNIFICANCE STATEMENTIn the nervous system, changes in activity that lead to modifications in synaptic structure and function are referred to as synaptic plasticity and are thought to be the basis of learning and memory. The secreted Wingless/Wnt molecule is a potent regulator of synaptic plasticity in both vertebrates and invertebrates. Understanding the molecular mechanisms that underlie these plastic changes is a major gap in our knowledge. Here, we identify a presynaptic effector molecule of the Wingless/Wnt signal, Cortactin. We show that this molecule is a potent regulator of modifications in synaptic structure and is necessary for the electrophysiological changes taking place during synaptic plasticity.
authors.affiliation: Institute of Neurobiology and.
authors.forename: Daniel
authors.identifier: 0000-0002-2568-9698
authors.initials: D
authors.lastname: Alicea
authors.affiliation: Institute of Neurobiology and.
authors.forename: Marizabeth
authors.identifier: 0000-0001-5738-4728
authors.initials: M
authors.lastname: Perez
authors.affiliation: Institute of Neurobiology and.|Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico 00901.
authors.forename: Carolina
authors.initials: C
authors.lastname: Maldonado
authors.affiliation: Institute of Neurobiology and.|Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico 00901.
authors.forename: Carihann
authors.initials: C
authors.lastname: Dominicci-Cotto
authors.affiliation: Institute of Neurobiology and bruno.marie@upr.edu.|Department of Anatomy and Neurobiology, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico 00901.
authors.forename: Bruno
authors.identifier: 0000-0002-6550-3851
authors.initials: B
authors.lastname: Marie
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006735:Horseradish Peroxidase / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051356:Cortactin; D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D050863:Synaptotagmin I; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; C070350:dlg1 protein, Drosophila; D011189:Potassium Chloride; D006735:Horseradish Peroxidase
keywords: NMJ; Wingless/Wnt; activity-dependent plasticity; miniature EPSP; synaptic plasticity