title: Multiple roles for frequenin/NCS-1 in synaptic function and development.
abstract: The calcium-binding protein frequenin (Frq), discovered in the fruit fly Drosophila, and its mammalian homologue neuronal calcium sensor 1 (NCS-1) have been reported to affect several aspects of synaptic transmission, including basal levels of neurotransmission and short- and long-term synaptic plasticities. However, discrepant reports leave doubts about the functional roles of these conserved proteins. In this review, we attempt to resolve some of these seemingly contradictory reports. We discuss how stimulation protocols, sources of calcium (voltage-gated channels versus internal stores), and expression patterns (presynaptic versus postsynaptic) of Frq may result in the activation of various protein targets, leading to different synaptic effects. In addition, the potential interactions of Frq's C-terminal and N-terminal domains with other proteins are discussed. Frq also has a role in regulating neurite outgrowth, axonal regeneration, and synaptic development. We examine whether the effects of Frq on neurotransmitter release and neurite outgrowth are distinct or interrelated through homeostatic mechanisms. Learning and memory are affected by manipulations of Frq probably through changes in synaptic transmission and neurite outgrowth, raising the possibility that Frq may be implicated in human pathological conditions, including schizophrenia, bipolar disorder, and X-linked mental retardation.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON, Canada, M5S 1A8. jeff.dason@utoronto.ca
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dason
authors.forename: Jesús
authors.initials: J
authors.lastname: Romero-Pozuelo
authors.forename: Harold L
authors.initials: HL
authors.lastname: Atwood
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferrús
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D019965:Neurocognitive Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051580:Neuronal Calcium-Sensor Proteins / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins