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Multiple Roles for Frequenin/NCS-1 in Synaptic Function and Development

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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.

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Acknowledgements

This work was supported by grants from CIHR, Canada MOP-37774 (H.L.A.) and MEC, Spain BFU2006-10180, and MYORES European Network CE: 511978 (A.F.). We would like to thank Dr. Milton Charlton for his help and advice on past and ongoing research projects related to this review.

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  1. Jesús Romero-Pozuelo

    Present address: Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M), Universidad Autónoma de Madrid, c/ Nicolás Cabrera 1, Madrid, 28049, Spain

Authors and Affiliations

  1. Department of Physiology, University of Toronto, Toronto, ON, Canada, M5S 1A8

    Jeffrey S. Dason & Harold L. Atwood

  2. Instituto Cajal, CSIC, Ave. Dr. Arce 37, Madrid, 28002, Spain

    Jesús Romero-Pozuelo & Alberto Ferrús

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  1. Jeffrey S. Dason
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Correspondence to Jeffrey S. Dason.

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Dason, J.S., Romero-Pozuelo, J., Atwood, H.L. et al. Multiple Roles for Frequenin/NCS-1 in Synaptic Function and Development. Mol Neurobiol 45, 388–402 (2012). https://doi.org/10.1007/s12035-012-8250-4

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