{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:28:53Z","timestamp":1772267333589,"version":"3.50.1"},"reference-count":89,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01EY010199"],"award-info":[{"award-number":["R01EY010199"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R21EY030785"],"award-info":[{"award-number":["R21EY030785"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,1,14]]},"abstract":"<jats:p>\n                    Neuronal health depends on quality control functions of autophagy, but mechanisms regulating neuronal autophagy are poorly understood. Previously, we showed that in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    starvation-independent quality control autophagy is regulated by acinus (acn) and the Cdk5-dependent phosphorylation of its serine\n                    <jats:sup>437<\/jats:sup>\n                    (Nandi et al., 2017). Here, we identify the phosphatase that counterbalances this activity and provides for the dynamic nature of acinus-serine\n                    <jats:sup>437<\/jats:sup>\n                    (acn-S437) phosphorylation. A genetic screen identified six phosphatases that genetically interacted with an acn gain-of-function model. Among these, loss of function of only one, the PPM-type phosphatase Nil (CG6036), enhanced pS437-acn levels. Cdk5-dependent phosphorylation of acn-S437 in\n                    <jats:italic>nil<\/jats:italic>\n                    <jats:sup>1<\/jats:sup>\n                    animals elevates neuronal autophagy and reduces the accumulation of polyQ proteins in a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    Huntington\u2019s disease model. Consistent with previous findings that Cd\n                    <jats:sup>2+<\/jats:sup>\n                    inhibits PPM-type phosphatases, Cd\n                    <jats:sup>2+<\/jats:sup>\n                    exposure elevated acn-S437 phosphorylation which was necessary for increased neuronal autophagy and protection against Cd\n                    <jats:sup>2+<\/jats:sup>\n                    -induced cytotoxicity. Together, our data establish the acn-S437 phosphoswitch as critical integrator of multiple stress signals regulating neuronal autophagy.\n                  <\/jats:p>","DOI":"10.7554\/elife.72169","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T08:00:35Z","timestamp":1642406435000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.72169","source":"Crossref","is-referenced-by-count":2,"title":["A phosphoswitch at acinus-serine437 controls autophagic responses to cadmium exposure and neurodegenerative stress"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-4943","authenticated-orcid":true,"given":"Nilay","family":"Nandi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, UT Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuhair","family":"Zaidi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, UT Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7769-4950","authenticated-orcid":true,"given":"Charles","family":"Tracy","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, UT Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1167-2676","authenticated-orcid":true,"given":"Helmut","family":"Kr\u00e4mer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, UT Southwestern Medical Center","place":["Dallas, United States"]},{"name":"Department of Cell Biology, UT Southwestern Medical Center","place":["Dallas, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4374","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1083\/jcb.201008119","type":"journal-article","article-title":"The full-of-bacteria gene is required for phagosome maturation during immune defense in Drosophila","volume":"192","author":"Akbar","year":"2011","journal-title":"The Journal of Cell Biology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1093\/oxfordjournals.molbev.a003823","type":"journal-article","article-title":"PPP family of protein Ser\/Thr phosphatases: two distinct branches?","volume":"18","author":"Andreeva","year":"2001","journal-title":"Molecular Biology and Evolution"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.ydbio.2006.02.046","type":"journal-article","article-title":"Alphabet, a Ser\/Thr phosphatase of the protein phosphatase 2C family, negatively regulates RAS\/MAPK signaling in Drosophila","volume":"294","author":"Baril","year":"2006","journal-title":"Developmental Biology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1534\/genetics.108.096461","type":"journal-article","article-title":"The PP2C Alphabet is a negative regulator of stress-activated protein kinase signaling in Drosophila","volume":"181","author":"Baril","year":"2009","journal-title":"Genetics"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1534\/genetics.117.1113","type":"journal-article","article-title":"Advances in Engineering the Fly Genome with the CRISPR-Cas System","volume":"208","author":"Bier","year":"2018","journal-title":"Genetics"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030177","type":"journal-article","article-title":"Genome-wide screen for modifiers of ataxin-3 neurodegeneration in Drosophila","volume":"3","author":"Bilen","year":"2007","journal-title":"PLOS Genetics"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.bbamcr.2018.12.011","type":"journal-article","article-title":"Drosophila Arl8 is a general positive regulator of lysosomal fusion events","volume":"1866","author":"Boda","year":"2019","journal-title":"Biochimica et Biophysica Acta. 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