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Citation
Wairkar, Y.P., Toda, H., Mochizuki, H., Furukubo-Tokunaga, K., Tomoda, T., DiAntonio, A. (2009). Unc-51 Controls Active Zone Density and Protein Composition by Downregulating ERK Signaling.  J. Neurosci. 29(2): 517--528.
FlyBase ID
FBrf0206580
Publication Type
Research paper
Abstract

Efficient synaptic transmission requires the apposition of neurotransmitter release sites opposite clusters of postsynaptic neurotransmitter receptors. Transmitter is released at active zones, which are composed of a large complex of proteins necessary for synaptic development and function. Many active zone proteins have been identified, but little is known of the mechanisms that ensure that each active zone receives the proper complement of proteins. Here we use a genetic analysis in Drosophila to demonstrate that the serine threonine kinase Unc-51 acts in the presynaptic motoneuron to regulate the localization of the active zone protein Bruchpilot opposite to glutamate receptors at each synapse. In the absence of Unc-51, many glutamate receptor clusters are unapposed to Bruchpilot, and ultrastructural analysis demonstrates that fewer active zones contain dense body T-bars. In addition to the presence of these aberrant synapses, there is also a decrease in the density of all synapses. This decrease in synaptic density and abnormal active zone composition is associated with impaired evoked transmitter release. Mechanistically, Unc-51 inhibits the activity of the MAP kinase ERK to promote synaptic development. In the unc-51 mutant, increased ERK activity leads to the decrease in synaptic density and the absence of Bruchpilot from many synapses. Hence, activated ERK negatively regulates synapse formation, resulting in either the absence of active zones or the formation of active zones without their proper complement of proteins. The Unc-51-dependent inhibition of ERK activity provides a potential mechanism for synapse-specific control of active zone protein composition and release probability.

PubMed ID
PubMed Central ID
PMC2741695 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Neurosci.
    Title
    Journal of Neuroscience
    Publication Year
    1981-
    ISBN/ISSN
    0270-6474 1529-2401
    Data From Reference
    Alleles (12)
    Genes (8)
    Natural transposons (1)
    Insertions (3)
    Transgenic Constructs (2)