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dc.contributor.authorWalldorf, Uwe
dc.contributor.authorXu, Ke
dc.contributor.authorZhong, Guisheng
dc.contributor.authorZhuang, Xiaowei
dc.contributor.authorBlunk, Aline Dorret
dc.contributor.authorAkbergenova, Yulia
dc.contributor.authorCho, Richard W.
dc.contributor.authorLee, Ji Hye
dc.contributor.authorLittleton, J. Troy
dc.date.accessioned2018-06-29T15:00:02Z
dc.date.available2018-06-29T15:00:02Z
dc.date.issued2014-07
dc.date.submitted2014-07
dc.identifier.issn1044-7431
dc.identifier.issn1095-9327
dc.identifier.urihttp://hdl.handle.net/1721.1/116694
dc.description.abstractSynaptic communication requires precise alignment of presynaptic active zones with postsynaptic receptors to enable rapid and efficient neurotransmitter release. How transsynaptic signaling between connected partners organizes this synaptic apparatus is poorly understood. To further define the mechanisms that mediate synapse assembly, we carried out a chemical mutagenesis screen in Drosophila to identify mutants defective in the alignment of active zones with postsynaptic glutamate receptor fields at the larval neuromuscular junction. From this screen we identified a mutation in Actin 57B that disrupted synaptic morphology and presynaptic active zone organization. Actin 57B, one of six actin genes in Drosophila, is expressed within the postsynaptic bodywall musculature. The isolated allele, actE84K, harbors a point mutation in a highly conserved glutamate residue in subdomain 1 that binds members of the Calponin Homology protein family, including spectrin. Homozygous actE84Kmutants show impaired alignment and spacing of presynaptic active zones, as well as defects in apposition of active zones to postsynaptic glutamate receptor fields. actE84Kmutants have disrupted postsynaptic actin networks surrounding presynaptic boutons, with the formation of aberrant actin swirls previously observed following disruption of postsynaptic spectrin. Consistent with a disruption of the postsynaptic actin cytoskeleton, spectrin, adducin and the PSD-95 homolog Discs-Large are all mislocalized in actE84Kmutants. Genetic interactions between actE84Kand neurexin mutants suggest that the postsynaptic actin cytoskeleton may function together with the Neurexin-Neuroligin transsynaptic signaling complex to mediate normal synapse development and presynaptic active zone organization. Keywords: Actin; Synapse; Spectrin; NMJ; Cytoskeleton; Neurexinen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant NS40296)en_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/J.MCN.2014.07.005en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titlePostsynaptic actin regulates active zone spacing and glutamate receptor apposition at the Drosophila neuromuscular junctionen_US
dc.typeArticleen_US
dc.identifier.citationBlunk, Aline D. et al. “Postsynaptic Actin Regulates Active Zone Spacing and Glutamate Receptor Apposition at the Drosophila Neuromuscular Junction.” Molecular and Cellular Neuroscience 61 (July 2014): 241–254 © 2014 Elsevier Incen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentPicower Institute for Learning and Memoryen_US
dc.contributor.mitauthorBlunk, Aline Dorret
dc.contributor.mitauthorAkbergenova, Yulia
dc.contributor.mitauthorCho, Richard W.
dc.contributor.mitauthorLee, Ji Hye
dc.contributor.mitauthorLittleton, J. Troy
dc.relation.journalMolecular and Cellular Neuroscienceen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-06-29T13:28:55Z
dspace.orderedauthorsBlunk, Aline D.; Akbergenova, Yulia; Cho, Richard W.; Lee, Jihye; Walldorf, Uwe; Xu, Ke; Zhong, Guisheng; Zhuang, Xiaowei; Littleton, J. Troyen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-5576-2887
mit.licensePUBLISHER_CCen_US


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