Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains
Name
Barber-2009-Postsynaptic regulat.pdf
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10.8 MB
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Checksum (MD5)
5930685d4d8b69afae8dc7b1a8513e5f
Author(s)
Littleton, J. Troy
Melom, Jan Elizabeth
Jorquera, Ramon
Barber, Cynthia F.
Date Issued
March 2009
Journal
Journal of Cell Biology
Publisher
The Rockefeller University Press
Citation
Barber, Cynthia F et al. “Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains.” The Journal of Cell Biology 187.2 (2009): 295-310. © 2010 by The Rockefeller University Press.
Version
Final published version
Abstract
Ca[superscript 2+] influx into synaptic compartments during activity is a key mediator of neuronal plasticity. Although the role of presynaptic Ca[superscript 2+] in triggering vesicle fusion though the Ca[superscript 2+] sensor synaptotagmin 1 (Syt 1) is established, molecular mechanisms that underlie responses to postsynaptic Ca[superscript 2+] 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 Ca[superscript 2+]–binding sites, as well as serine 284, an evolutionarily conserved substitution for a key Ca[superscript 2+]-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 Ca[superscript 2+] sensor for presynaptic vesicle fusion.
Subjects
United States National Institutes of Healt (Grant NS40296)
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Attribution-Noncommercial-Share Alike 3.0 Unported
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DOI of Published Version
http://dx.doi.org/10.1083/jcb.200903098
