title: Phosphorylation of Complexin by PKA Regulates Activity-Dependent Spontaneous Neurotransmitter Release and Structural Synaptic Plasticity.
abstract: Synaptic plasticity is a fundamental feature of the nervous system that allows adaptation to changing behavioral environments. Most studies of synaptic plasticity have examined the regulated trafficking of postsynaptic glutamate receptors that generates alterations in synaptic transmission. Whether and how changes in the presynaptic release machinery contribute to neuronal plasticity is less clear. The SNARE complex mediates neurotransmitter release in response to presynaptic Ca(2+) entry. Here we show that the SNARE fusion clamp Complexin undergoes activity-dependent phosphorylation that alters the basic properties of neurotransmission in Drosophila. Retrograde signaling following stimulation activates PKA-dependent phosphorylation of the Complexin C terminus that selectively and transiently enhances spontaneous release. Enhanced spontaneous release is required for activity-dependent synaptic growth. These data indicate that SNARE-dependent fusion mechanisms can be regulated in an activity-dependent manner and highlight the key role of spontaneous neurotransmitter release as a mediator of functional and structural plasticity.
authors.affiliation: Department of Biology and Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: rcho@mit.edu.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Cho
authors.affiliation: Department of Biology and Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Buhl
authors.affiliation: Department of Biology and Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Volfson
authors.affiliation: Department of Biology and Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Tran
authors.affiliation: Department of Cell Biology, Nanobiology Institute, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Biology and Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Akbergenova
authors.affiliation: Department of Biology and Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: J Troy
authors.initials: JT
authors.lastname: Littleton
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005089:Exocytosis / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010766:Phosphorylation; D050600:SNARE Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050600:SNARE Proteins; C000605369:cpx protein, Drosophila; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium
keywords: Exocytosis; Neurotransmitter Release; SNARE complex; Synapse; minis; retrograde signaling; spontaneous release