title: A genetic analysis of synaptic development: pre- and postsynaptic dCBP control transmitter release at the Drosophila NMJ.
abstract: Postsynaptic dCBP (Drosophila homolog of the CREB binding protein) is required for presynaptic functional development. Viable, hypomorphic dCBP mutations have a approximately 50% reduction in presynaptic transmitter release without altering the Ca2+ cooperativity of release or synaptic ultrastructure (total bouton number is increased by 25%-30%). Exogenous expression of dCBP in muscle rescues impaired presynaptic release in the dCBP mutant background, while presynaptic dCBP expression does not. In addition, overexpression experiments indicate that elevated dCBP can also inhibit presynaptic functional development in a manner distinct from the effects of dCBP loss of function. Pre- or postsynaptic overexpression of dCBP (in wild type) reduces presynaptic release. However, we do not observe an increase in bouton number, and presynaptic overexpression impairs short-term facilitation. These data suggest that dCBP participates in a postsynaptic regulatory system that controls functional synaptic development.
authors.affiliation: Department of Biochemistry and Biophysics, University of California Medical School, San Francisco 94143, USA.
authors.forename: K W
authors.initials: KW
authors.lastname: Marek
authors.forename: N
authors.initials: N
authors.lastname: Ng
authors.forename: R
authors.initials: R
authors.lastname: Fetter
authors.forename: S
authors.initials: S
authors.lastname: Smolik
authors.forename: C S
authors.initials: CS
authors.lastname: Goodman
authors.forename: G W
authors.initials: GW
authors.lastname: Davis
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000235:genetics; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D009154:Mutation / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism*; D013569:Synapses / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein