{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:37:05Z","timestamp":1778683025482,"version":"3.51.4"},"reference-count":133,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T00:00:00Z","timestamp":1633737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Tuberous Sclerosis Foundation","award":["TH 1358\/3-1"],"award-info":[{"award-number":["TH 1358\/3-1"]}]},{"name":"PoLiMeR 737 Innovative Training Network","award":["Marie Sklodowska-Curie grant agreement 812616"],"award-info":[{"award-number":["Marie Sklodowska-Curie grant agreement 812616"]}]},{"name":"MESI-STRAT project","award":["grant agreement 738 754688"],"award-info":[{"award-number":["grant agreement 738 754688"]}]},{"name":"Doktoratskolleg - BIDOC Eurac\/Medical University Innsbruck","award":["D-151660-018-017"],"award-info":[{"award-number":["D-151660-018-017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Seizure threshold 2 (SZT2) is a component of the KICSTOR complex which, under catabolic conditions, functions as a negative regulator in the amino acid-sensing branch of mTORC1. Mutations in this gene cause a severe neurodevelopmental and epileptic encephalopathy whose main symptoms include epilepsy, intellectual disability, and macrocephaly. As SZT2 remains one of the least characterized regulators of mTORC1, in this work we performed a systematic interactome analysis under catabolic and anabolic conditions. Besides numerous mTORC1 and AMPK signaling components, we identified clusters of proteins related to autophagy, ciliogenesis regulation, neurogenesis, and neurodegenerative processes. Moreover, analysis of SZT2 ablated cells revealed increased mTORC1 signaling activation that could be reversed by Rapamycin or Torin treatments. Strikingly, SZT2 KO cells also exhibited higher levels of autophagic components, independent of the physiological conditions tested. These results are consistent with our interactome data, in which we detected an enriched pool of selective autophagy receptors\/regulators. Moreover, preliminary analyses indicated that SZT2 alters ciliogenesis. Overall, the data presented form the basis to comprehensively investigate the physiological functions of SZT2 that could explain major molecular events in the pathophysiology of developmental and epileptic encephalopathy in patients with SZT2 mutations.<\/jats:p>","DOI":"10.3390\/cells10102711","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:19:32Z","timestamp":1633900772000},"page":"2711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The SZT2 Interactome Unravels New Functions of the KICSTOR Complex"],"prefix":"10.3390","volume":"10","author":[{"given":"Cecilia","family":"Cattelani","sequence":"first","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of L\u00fcbeck, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Lesiak","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gudrun","family":"Liebscher","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-1323","authenticated-orcid":false,"given":"Isabel I.","family":"Singer","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taras","family":"Stasyk","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz H.","family":"Walln\u00f6fer","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-8707","authenticated-orcid":false,"given":"Alexander M.","family":"Heberle","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Laboratory of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrado","family":"Corti","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of L\u00fcbeck, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-3553","authenticated-orcid":false,"given":"Michael W.","family":"Hess","sequence":"additional","affiliation":[{"name":"Institute of Histology and Embryology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Pfaller","sequence":"additional","affiliation":[{"name":"Institute of Histology and Embryology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5804-6031","authenticated-orcid":false,"given":"Marcel","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter P.","family":"Pramstaller","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of L\u00fcbeck, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A.","family":"Hicks","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of L\u00fcbeck, 39100 Bolzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Thedieck","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Laboratory of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands"},{"name":"Department for Neuroscience, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8908-5589","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1116-2120","authenticated-orcid":false,"given":"Lukas A.","family":"Huber","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Austrian Drug Screening Institute, ADSI, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0576-2680","authenticated-orcid":false,"given":"Mariana","family":"Eca Guimaraes de Araujo","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/j.1601-183X.2009.00509.x","article-title":"Szt2, a novel gene for seizure threshold in mice","volume":"8","author":"Frankel","year":"2009","journal-title":"Genes Brain Behav."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.freeradbiomed.2009.12.023","article-title":"A novel giant peroxisomal superoxide dismutase motif-containing protein","volume":"48","author":"Toutzaris","year":"2010","journal-title":"Free 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