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dc.contributor.authorAcharya, Kalpana D.en_US
dc.contributor.authorNettles, Sabin A.en_US
dc.contributor.authorSellers, Katherine J.en_US
dc.contributor.authorIm, Dana D.en_US
dc.contributor.authorHarling, Moriahen_US
dc.contributor.authorPattanayak, Cassandraen_US
dc.contributor.authorVardar-Ulu, Didemen_US
dc.contributor.authorLichti, Cheryl F.en_US
dc.contributor.authorHuang, Shixiaen_US
dc.contributor.authorEdwards, Dean P.en_US
dc.contributor.authorSrivastava, Deepak P.en_US
dc.contributor.authorDenner, Larryen_US
dc.contributor.authorTetel, Marc J.en_US
dc.coverage.spatialUnited Statesen_US
dc.date2017-09-01
dc.date.accessioned2019-09-09T15:13:49Z
dc.date.available2019-09-09T15:13:49Z
dc.date.issued2017-09
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28955722
dc.identifier.citationKalpana D Acharya, Sabin A Nettles, Katherine J Sellers, Dana D Im, Moriah Harling, Cassandra Pattanayak, Didem Vardar-Ulu, Cheryl F Lichti, Shixia Huang, Dean P Edwards, Deepak P Srivastava, Larry Denner, Marc J Tetel. 2017. "The Progestin Receptor Interactome in the Female Mouse Hypothalamus: Interactions with Synaptic Proteins Are Isoform Specific and Ligand Dependent.." eNeuro, Volume 4, Issue 5, https://doi.org/10.1523/ENEURO.0272-17.2017
dc.identifier.issn2373-2822
dc.identifier.urihttps://hdl.handle.net/2144/37750
dc.description.abstractProgestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase-tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I-positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease.en_US
dc.description.sponsorshipMR/L021064/1 - Medical Research Council; R01 DK061935 - NIDDK NIH HHS; P30 CA125123 - NCI NIH HHSen_US
dc.languageeng
dc.language.isoen_US
dc.relation.ispartofeNeuro
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectCortexen_US
dc.subjectEstrogenen_US
dc.subjectProgesteroneen_US
dc.subjectProteomicsen_US
dc.subjectSynapseen_US
dc.subjectSynapsinen_US
dc.subjectAnimalsen_US
dc.subjectCells, cultureden_US
dc.subjectCerebral cortexen_US
dc.subjectEmbryo, mammalianen_US
dc.subjectEstradiolen_US
dc.subjectFemaleen_US
dc.subjectGene expression regulationen_US
dc.subjectGlutathione transferaseen_US
dc.subjectHypothalamusen_US
dc.subjectLigandsen_US
dc.subjectMiceen_US
dc.subjectMice, inbred C57BLen_US
dc.subjectNerve tissue proteinsen_US
dc.subjectNeuronsen_US
dc.subjectOvariectomyen_US
dc.subjectProtein bindingen_US
dc.subjectProtein isoformsen_US
dc.subjectReceptors, progesteroneen_US
dc.subjectSignal transductionen_US
dc.subjectTranscription, geneticen_US
dc.titleThe progestin receptor interactome in the female mouse hypothalamus: interactions with synaptic proteins are isoform specific and ligand dependenten_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1523/ENEURO.0272-17.2017
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.mycv284749


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