{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:13:48Z","timestamp":1791220428378,"version":"4.1.0"},"reference-count":72,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS098243"],"award-info":[{"award-number":["R01NS098243"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS100008"],"award-info":[{"award-number":["R01NS100008"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS078504"],"award-info":[{"award-number":["R01NS078504"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS046535"],"award-info":[{"award-number":["R01NS046535"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Robert Packard Center for ALS Research at Johns Hopkins","award":["17-IIP-356-1"],"award-info":[{"award-number":["17-IIP-356-1"]}]},{"DOI":"10.13039\/100000971","name":"The ALS Association","doi-asserted-by":"crossref","award":["17-IIP-356-1"],"award-info":[{"award-number":["17-IIP-356-1"]}],"id":[{"id":"10.13039\/100000971","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,30]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Mutations in\n                    <jats:italic>UBQLN2<\/jats:italic>\n                    cause amyotrophic lateral sclerosis with frontotemporal dementia (ALS\/FTD). UBQLN2 regulates proteostasis by clearing misfolded proteins from cells through the proteasome and autophagy degradation pathways. Here, we report on defects in autophagy that results from knockout or expression of WT and ALS\/FTD mutant UBQLN2 proteins in cells and mice. We show that loss of UBQLN2 reduces expression of ATP6v1g1, a critical subunit of the ATPase pump that regulates vacuolar acidification and is required for the maturation of autophagosomes. We show that WT but not ALS\/FTD mutant UBQLN2 proteins can rescue the acidification defect. Furthermore, WT but not ALS\/FTD mutant UBQLN2 proteins bind and stimulate ATP6v1g1 biogenesis, suggesting an important role played by UBQLN2 in V-ATPase regulation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1917371117","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T20:35:04Z","timestamp":1591648504000},"page":"15230-15241","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":88,"title":["ALS\/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function"],"prefix":"10.1073","volume":"117","author":[{"given":"Josephine J.","family":"Wu","sequence":"first","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Cai","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie E.","family":"Greenslade","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole R.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Fan","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0528-8114","authenticated-orcid":false,"given":"Nhat T. T.","family":"Le","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Tatman","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Whiteley","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4914-1619","authenticated-orcid":false,"given":"Miguel A.","family":"Prado","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9392-3327","authenticated-orcid":false,"given":"Birger V.","family":"Dieriks","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Medical Imaging, University of Auckland, 1010 Auckland, New Zealand;"},{"name":"Centre for Brain Research, University of Auckland, 1010 Auckland, New Zealand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice A.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Medical Imaging, University of Auckland, 1010 Auckland, New Zealand;"},{"name":"Centre for Brain Research, University of Auckland, 1010 Auckland, New Zealand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Shaw","sequence":"additional","affiliation":[{"name":"United Kingdom Dementia Research Institute, King\u2019s College London, WC2R 2LS London, United Kingdom;"},{"name":"Maurice Wohl Clinical Neuroscience Institute, King\u2019s College London, SE5 9RT London, United Kingdom;"},{"name":"Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London, WC2R 2LS London, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teepu","family":"Siddique","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-9498","authenticated-orcid":false,"given":"Richard L. M.","family":"Faull","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Medical Imaging, University of Auckland, 1010 Auckland, New Zealand;"},{"name":"Centre for Brain Research, University of Auckland, 1010 Auckland, New Zealand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-3599","authenticated-orcid":false,"given":"Emma L.","family":"Scotter","sequence":"additional","affiliation":[{"name":"Centre for Brain Research, University of Auckland, 1010 Auckland, New Zealand;"},{"name":"Department of Pharmacology and Clinical Pharmacology, University of Auckland, 1010 Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Finley","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervyn J.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Center for Biomedical Engineering and Technology, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10353"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2018.03.001"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2019.05.006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt243"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00119"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25453"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80212-9"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.4.847"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00122-0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00040-X"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.12.008"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01135-2"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.001"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.04.031"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2004-6109"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130162"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.01.021"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2019.06.002"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.243147"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-08-0775"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq231"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2013.22"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0281-x"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.238"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-0970-z"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.06.019"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.08.015"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.05.008"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060614-033955"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.8b00516"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702824200"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2697"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0003-4"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.02.005"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405741111"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12606"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1367-y"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608432113"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.035"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.026"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47429-2"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18091865"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.2144\/000113519"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.2144\/000113943"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.02.004"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811997115"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220849"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.4.11863"},{"key":"e_1_3_4_49_2","first-page":"845","article-title":"Common pathobiochemical hallmarks of progranulin-associated frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis","volume":"127","author":"G\u00f6tzl J. K.","year":"2014","unstructured":"J. K. G\u00f6tzl ., Common pathobiochemical hallmarks of progranulin-associated frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis. Acta Neuropathol. 127, 845\u2013860 (2014).","journal-title":"Acta Neuropathol."},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv020"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810522115"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.158550"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.05.015"},{"key":"e_1_3_4_54_2","first-page":"2697","article-title":"RILP regulates vacuolar ATPase through interaction with the V1G1 subunit","volume":"127","author":"De Luca M.","year":"2014","unstructured":"M. De Luca ., RILP regulates vacuolar ATPase through interaction with the V1G1 subunit. J. Cell Sci. 127, 2697\u20132708 (2014).","journal-title":"J. Cell Sci."},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26787"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601441200"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00340.2006"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2014.01.018"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.2.575-589.2005"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.020"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26435"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25880"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.4149"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-017-0024-9"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060441"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2019.03.012"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00263"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704294114"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40811"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.05.008"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0578-19.2019"},{"key":"e_1_3_4_72_2","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council","year":"2011","unstructured":"National Research Council, Guide for the Care and Use of Laboratory Animals (National Academies Press, Washington, DC, ed. 8, 2011).","edition":"8"}],"updated-by":[{"DOI":"10.1073\/pnas.2114051118","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1917371117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1917371117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T04:42:06Z","timestamp":1649824926000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1917371117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,8]]},"references-count":72,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2020,6,30]]}},"alternative-id":["10.1073\/pnas.1917371117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1917371117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,8]]},"assertion":[{"value":"2020-06-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}