{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:28:19Z","timestamp":1793413699571,"version":"4.5.0"},"reference-count":67,"publisher":"National Academy of Sciences","issue":"5","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007795","name":"Stowers Institute for Medical Research","doi-asserted-by":"publisher","award":["SIMR"],"award-info":[{"award-number":["SIMR"]}],"id":[{"id":"10.13039\/100007795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:p>\n                    Memory requires experience-dependent alterations in the synaptic proteome. Chaperones interface between the environment and the proteome. Manipulating J-domain protein (JDP) chaperones, the most diverse family of chaperones, in a\n                    <jats:italic toggle=\"yes\">Drosophila<\/jats:italic>\n                    neuronal circuit that encodes associative long-term memories, we identified yet uncharacterized JDPs that transduce sensory cues. One of these JDPs, CG10375, which we named Funes, enhances memory when overexpressed and impairs memory when functionally impaired. Funes overexpression enhances memory formation even when sensory stimuli are suboptimal. At the circuit level, Funes acts on neurons where conditioned and unconditioned stimuli converge to form associative memories. From a proteomic-based screen, we found that overexpression of Funes changes the solubility of a small subset of proteins, one of which is the mRNA-binding protein Orb2. Combining in vitro and in vivo biophysical, biochemical, and cryo-EM structural analyses, we found that Funes associates with oligomeric Orb2 and promotes the formation of translationally active amyloids. Perturbation of the conserved J domain eliminates the ability of Funes to facilitate amyloid assembly and promote memory. We posit that the brain harbors chaperones that influence memory by regulating physiological amyloid formation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2516310123","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:06:26Z","timestamp":1769792786000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["A J-domain protein enhances memory by promoting physiological amyloid formation in\n                    <i>Drosophila<\/i>"],"prefix":"10.1073","volume":"123","author":[{"given":"Kyle","family":"Patton","sequence":"first","affiliation":[{"name":"Stowers Institute for Medical Research","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4066-6818","authenticated-orcid":false,"given":"Yangyang","family":"Yi","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong","place":["Pokfulam, Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Burt","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research","place":["Kansas City"]},{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1483-9658","authenticated-orcid":false,"given":"Kevin Kan-Shing","family":"Ng","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong","place":["Pokfulam, Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5626-3198","authenticated-orcid":false,"given":"Mayur","family":"Mukhi","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong","place":["Pokfulam, Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-8800","authenticated-orcid":false,"given":"Peerzada Shariq Shaheen","family":"Khaki","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong","place":["Pokfulam, Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6393-6058","authenticated-orcid":false,"given":"Ruben","family":"Hervas","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Hong Kong","place":["Pokfulam, Hong Kong"]},{"name":"School of Biomedical Engineering, The University of Hong Kong","place":["Pokfulam, Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-6273","authenticated-orcid":false,"given":"Kausik","family":"Si","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research","place":["Kansas City"]},{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center","place":["Kansas City"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005751"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2020.137036"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128976"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060208-092442"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2941"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-018-0948-4"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13076"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808934105"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.10.2435"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201593489"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.02.003"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.03.017"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.06.015"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.19.2811"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25635-y"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/378632a0"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm6063"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28341-w"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202113952"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.08.006"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1657108"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.10.052"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.11.040"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.05.037"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.004"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2000.4221"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9CS00199A"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2022.167919"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.019"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.032"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba3526"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.05.021"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1996"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.008"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1074"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.5.1482"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2009.00482.x"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227170"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2011.03.032"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04577"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-080317-0621333"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04580"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421930112"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.01.036"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404458200"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.09.054"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.020"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004433107"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603715113"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0534"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0231-1"},{"key":"e_1_3_4_52_2","first-page":"210","article-title":"Schizophrenia-associated methylomic variation: Molecular signatures of disease and polygenic risk burden across multiple brain regions","volume":"26","author":"Viana J.","year":"2017","unstructured":"J. Viana , Schizophrenia-associated methylomic variation: Molecular signatures of disease and polygenic risk burden across multiple brain regions. Hum. Mol. Genet. 26, 210\u2013225 (2017).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2021.04.014"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.02.033"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2012.09.015"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.03.152"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.01.001"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08324-z"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00842-09"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002585"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01011-0"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.006"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001786"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.10.032"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.010"},{"key":"e_1_3_4_66_2","doi-asserted-by":"crossref","unstructured":"R. Hervas K. Si Funes-induced Orb2 amyloid like endogenous Orb2 amyloid. Electron Microscopy Database. https:\/\/www.ebi.ac.uk\/emdb\/EMD-39095. Deposited 8 February 2024.","DOI":"10.2210\/pdb8yac\/pdb"},{"key":"e_1_3_4_67_2","doi-asserted-by":"crossref","unstructured":"R. Hervas K. Si Funes-induced Orb2 amyloid like endogenous Orb2 amyloid. Protein Data Bank. https:\/\/www.rcsb.org\/structure\/8YAC. Deposited 8 February 2024.","DOI":"10.2210\/pdb8yac\/pdb"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2516310123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:06:28Z","timestamp":1769792788000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2516310123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":67,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,2,3]]}},"alternative-id":["10.1073\/pnas.2516310123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2516310123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"2025-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2516310123"}}