Shank3 is part of a zinc-sensitive signalling system that regulates excitatory synaptic strength

Show simple item record Arons, MH en Lee, Kevin en Thynne, CJ en Kim, SA en Schob, C en Kindler, S en Montgomery, Johanna en Garner, C en 2017-10-16T02:02:20Z en 2016-08-31 en
dc.identifier.citation Journal of Neuroscience 36(35):9124-9134 31 Aug 2016 en
dc.identifier.issn 0270-6474 en
dc.identifier.uri en
dc.description.abstract Shank3 is a multidomain scaffold protein localized to the postsynaptic density of excitatory synapses. Functional studies in vivo and in vitro support the concept that Shank3 is critical for synaptic plasticity and the trans-synaptic coupling between the reliability of presynaptic neurotransmitter release and postsynaptic responsiveness. However, how Shank3 regulates synaptic strength remains unclear. The C terminus of Shank3 contains a sterile alpha motif (SAM) domain that is essential for its postsynaptic localization and also binds zinc, thus raising the possibility that changing zinc levels modulate Shank3 function in dendritic spines. In support of this hypothesis, we find that zinc is a potent regulator of Shank3 activation and dynamics in rat hippocampal neurons. Moreover, we show that zinc modulation of synaptic transmission is Shank3 dependent. Interestingly, an autism spectrum disorder (ASD)-associated variant of Shank3 (Shank3R87C) retains its zinc sensitivity and supports zinc-dependent activation of AMPAR-mediated synaptic transmission. However, elevated zinc was unable to rescue defects in trans-synaptic signaling caused by the R87C mutation, implying that trans-synaptic increases in neurotransmitter release are not necessary for the postsynaptic effects of zinc. Together, these data suggest that Shank3 is a key component of a zinc-sensitive signaling system, regulating synaptic strength that may be impaired in ASD. en
dc.publisher Society for Neuroscience en
dc.relation.ispartofseries Journal of Neuroscience en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title Shank3 is part of a zinc-sensitive signalling system that regulates excitatory synaptic strength en
dc.type Journal Article en
dc.identifier.doi 10.1523/JNEUROSCI.0116-16.2016 en
pubs.issue 35 en
pubs.begin-page 9124 en
pubs.volume 36 en
dc.rights.holder Copyright: Society for Neuroscience en
dc.identifier.pmid 27581454 en
pubs.end-page 9134 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 540834 en Medical and Health Sciences en Medical Sciences en Physiology Division en
dc.identifier.eissn 1529-2401 en
pubs.record-created-at-source-date 2016-09-07 en
pubs.dimensions-id 27581454 en

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