Epsin 1 Promotes Synaptic Growth by Enhancing BMP Signal Levels in Motoneuron Nuclei

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dc.contributor.authorPhillip A. Vanlandinghamen_US
dc.contributor.authorTaylor R. Foreen_US
dc.contributor.authorLerin R. Chastainen_US
dc.contributor.authorSuzanne M. Royeren_US
dc.contributor.authorHong Baoen_US
dc.contributor.authorNoreen E. Reisten_US
dc.contributor.authorBing Zhangen_US
dc.date.accessioned2015-01-23T17:17:46Z
dc.date.accessioned2016-03-30T15:36:11Z
dc.date.available2015-01-23T17:17:46Z
dc.date.available2016-03-30T15:36:11Z
dc.date.issued2013-06-19en_US
dc.descriptionWe thank Carl-Henrik Heldin (Uppsala University, Sweden) for his generous gift of the PS1 pMad antibody, Hugo Bellen, Corey Goodman, Janis Fischer, Graeme Davis, Guillermo Marques, Michael O'Connor, Kate O'Connor-Giles, and the Bloomington Drosophila Stock Center for flies strains, the Developmental Studies Hybridoma Bank at the University of Iowa for antibodies to Wit and CSP; Marie Phillips for advice on membrane fractionation; Avital Rodal, Kate O'Connor-Giles, Ela Serpe, Kristi Wharton, Mojgan Padash-Barmchi for discussions or comments on the manuscript. We also thank Jody Summers at OUHSC for her generosity in letting us to use her confocal microscope.en_US
dc.descriptionConceived and designed the experiments: PAV TRF LRC BZ. Performed the experiments: PAV TRF LRC SMR HB NER BZ. Analyzed the data: PAV TRF LRC SMR HB NER BZ. Wrote the paper: PAV TRF BZ.en_US
dc.description.abstractBone morphogenetic protein (BMP) retrograde signaling is crucial for neuronal development and synaptic plasticity. However, how the BMP effector phospho-Mother against decapentaplegic (pMad) is processed following receptor activation remains poorly understood. Here we show that Drosophila Epsin1/Liquid facets (Lqf) positively regulates synaptic growth through post-endocytotic processing of pMad signaling complex. Lqf and the BMP receptor Wishful thinking (Wit) interact genetically and biochemically. lqf loss of function (LOF) reduces bouton number whereas overexpression of lqf stimulates bouton growth. Lqf-stimulated synaptic overgrowth is suppressed by genetic reduction of wit. Further, synaptic pMad fails to accumulate inside the motoneuron nuclei in lqf mutants and lqf suppresses synaptic overgrowth in spinster (spin) mutants with enhanced BMP signaling by reducing accumulation of nuclear pMad. Interestingly, lqf mutations reduce nuclear pMad levels without causing an apparent blockage of axonal transport itself. Finally, overexpression of Lqf significantly increases the number of multivesicular bodies (MVBs) in the synapse whereas lqf LOF reduces MVB formation, indicating that Lqf may function in signaling endosome recycling or maturation. Based on these observations, we propose that Lqf plays a novel endosomal role to ensure efficient retrograde transport of BMP signaling endosomes into motoneuron nuclei.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationVanlandingham PA, Fore TR, Chastain LR, Royer SM, Bao H, et al. (2013) Epsin 1 Promotes Synaptic Growth by Enhancing BMP Signal Levels in Motoneuron Nuclei. PLoS ONE 8(6): e65997. doi:10.1371/journal.pone.0065997en_US
dc.identifier.doi10.1371/journal.pone.0065997en_US
dc.identifier.urihttp://hdl.handle.net/11244/14094
dc.language.isoen_USen_US
dc.publisherPLos Oneen_US
dc.relation.ispartofseriesPLoS ONE 8(6):e65997en_US
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065997en_US
dc.rightsAttribution 3.0 United Statesen_US
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/en_US
dc.subjectPLOSen_US
dc.subjectPublic Library of Scienceen_US
dc.subjectOpen Accessen_US
dc.subjectOpen-Accessen_US
dc.subjectScienceen_US
dc.subjectMedicineen_US
dc.subjectBiologyen_US
dc.subjectResearchen_US
dc.subjectPeer-reviewen_US
dc.subjectInclusiveen_US
dc.subjectInterdisciplinaryen_US
dc.subjectAnte-disciplinaryen_US
dc.subjectPhysicsen_US
dc.subjectChemistryen_US
dc.subjectEngineeringen_US
dc.titleEpsin 1 Promotes Synaptic Growth by Enhancing BMP Signal Levels in Motoneuron Nucleien_US
dc.typeResearch Articleen_US

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