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Published online
doi:10.1083/jcb.200903098
The Journal of Cell Biology, Vol. 187, No. 2, 295-310
The Rockefeller University Press, 0021-9525 $30.00
© Barber et al.
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Article

Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains



Cynthia F. Barber1,2, Ramon A. Jorquera1,2, Jan E. Melom1,2, and J. Troy Littleton1,2

1 Department of Biology and 2 Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139

Correspondence to J. Troy Littleton: troy{at}mit.edu

Ca2+ influx into synaptic compartments during activity is a key mediator of neuronal plasticity. Although the role of presynaptic Ca2+ in triggering vesicle fusion though the Ca2+ sensor synaptotagmin 1 (Syt 1) is established, molecular mechanisms that underlie responses to postsynaptic Ca2+ influx remain unclear. In this study, we demonstrate that fusion-competent Syt 4 vesicles localize postsynaptically at both neuromuscular junctions (NMJs) and central nervous system synapses in Drosophila melanogaster. Syt 4 messenger RNA and protein expression are strongly regulated by neuronal activity, whereas altered levels of postsynaptic Syt 4 modify synaptic growth and presynaptic release properties. Syt 4 is required for known forms of activity-dependent structural plasticity at NMJs. Synaptic proliferation and retrograde signaling mediated by Syt 4 requires functional C2A and C2B Ca2+–binding sites, as well as serine 284, an evolutionarily conserved substitution for a key Ca2+-binding aspartic acid found in other synaptotagmins. These data suggest that Syt 4 regulates activity-dependent release of postsynaptic retrograde signals that promote synaptic plasticity, similar to the role of Syt 1 as a Ca2+ sensor for presynaptic vesicle fusion.


Abbreviations used in this paper: {alpha}-Cpx, {alpha}-complexin; ANOVA, analysis of variance; Brp, Bruchpilot; CNS, central nervous system; EPSC, excitatory postsynaptic current; mRFP, monomeric RFP; NMJ, neuromuscular junction; VNC, ventral nerve cord.

© 2009 Barber et al.
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