[{"publication":"Nature Communications","language":[{"iso":"eng"}],"isi":1,"has_accepted_license":"1","intvolume":"        12","issue":"1","article_processing_charge":"No","oa":1,"date_updated":"2024-09-10T12:04:26Z","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","status":"public","type":"journal_article","publication_identifier":{"eissn":["2041-1723"]},"month":"05","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"creator":"kschuh","file_size":9358599,"relation":"main_file","content_type":"application/pdf","access_level":"open_access","success":1,"file_name":"2021_NatureCommunications_Morandell.pdf","checksum":"337e0f7959c35ec959984cacdcb472ba","file_id":"9430","date_created":"2021-05-28T12:39:43Z","date_updated":"2021-05-28T12:39:43Z"}],"day":"24","oa_version":"Published Version","author":[{"full_name":"Morandell, Jasmin","first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Lena A","full_name":"Schwarz, Lena A","last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Bernadette","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"orcid":"0000-0003-1671-393X","last_name":"Tasciyan","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren","first_name":"Saren"},{"orcid":"0000-0001-8370-6161","last_name":"Dimchev","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","full_name":"Dimchev, Georgi A","first_name":"Georgi A"},{"first_name":"Armel","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas"},{"orcid":"0000-0003-1216-9105","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","first_name":"Christoph M"},{"full_name":"Kreuzinger, Caroline","first_name":"Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","first_name":"Christoph"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","full_name":"Knaus, Lisa","first_name":"Lisa"},{"full_name":"Dobler, Zoe","first_name":"Zoe","last_name":"Dobler","id":"D23090A2-9057-11EA-883A-A8396FC7A38F"},{"last_name":"Cacci","first_name":"Emanuele","full_name":"Cacci, Emanuele"},{"first_name":"Florian KM","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"doi":"10.1038/s41467-021-23123-x","_id":"9429","article_type":"original","file_date_updated":"2021-05-28T12:39:43Z","acknowledged_ssus":[{"_id":"PreCl"}],"related_material":{"record":[{"status":"public","relation":"earlier_version","id":"7800"},{"status":"public","id":"12401","relation":"dissertation_contains"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/"}]},"article_number":"3058","ec_funded":1,"year":"2021","acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","keyword":["General Biochemistry","Genetics and Molecular Biology"],"date_created":"2021-05-28T11:49:46Z","citation":{"apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>."},"date_published":"2021-05-24T00:00:00Z","publisher":"Springer Nature","quality_controlled":"1","volume":12,"department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["572"],"abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.","lang":"eng"}],"external_id":{"isi":["000658769900010"]},"publication_status":"published"},{"acknowledged_ssus":[{"_id":"PreCl"}],"file_date_updated":"2020-07-14T12:48:03Z","_id":"7800","doi":"10.1101/2020.01.10.902064 ","date_created":"2020-05-05T14:31:33Z","citation":{"chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>.","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>"},"year":"2020","related_material":{"record":[{"relation":"dissertation_contains","id":"8620","status":"public"},{"id":"9429","relation":"later_version","status":"public"}]},"project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF"}],"department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"publisher":"Cold Spring Harbor Laboratory","date_published":"2020-01-11T00:00:00Z","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","publication_status":"submitted","abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.","lang":"eng"}],"ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"language":[{"iso":"eng"}],"publication":"bioRxiv","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","date_updated":"2024-09-10T12:04:26Z","oa":1,"article_processing_charge":"No","has_accepted_license":"1","status":"public","type":"preprint","author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","full_name":"Morandell, Jasmin","first_name":"Jasmin"},{"last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A","first_name":"Lena A"},{"last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","full_name":"Basilico, Bernadette"},{"last_name":"Tasciyan","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","first_name":"Saren"},{"first_name":"Armel","full_name":"Nicolas, Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Christoph M","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","orcid":"0000-0003-1216-9105"},{"full_name":"Kreuzinger, Caroline","first_name":"Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Lisa","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus"},{"last_name":"Dobler","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","first_name":"Zoe"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","full_name":"Danzl, Johann G","first_name":"Johann G"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"day":"11","oa_version":"Preprint","file":[{"creator":"rsix","content_type":"application/pdf","access_level":"open_access","file_size":2931370,"relation":"main_file","file_id":"7801","file_name":"2020.01.10.902064v1.full.pdf","checksum":"c6799ab5daba80efe8e2ed63c15f8c81","date_created":"2020-05-05T14:31:19Z","date_updated":"2020-07-14T12:48:03Z"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01"},{"language":[{"iso":"eng"}],"_id":"7415","article_type":"original","doi":"10.1016/j.euroneuro.2019.09.040","publication":"European Neuropsychopharmacology","citation":{"apa":"Morandell, J., Nicolas, A., Schwarz, L. A., &#38; Novarino, G. (2019). S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. <i>European Neuropsychopharmacology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">https://doi.org/10.1016/j.euroneuro.2019.09.040</a>","short":"J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12.","ama":"Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. <i>European Neuropsychopharmacology</i>. 2019;29(Supplement 6):S11-S12. doi:<a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">10.1016/j.euroneuro.2019.09.040</a>","ieee":"J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism,” <i>European Neuropsychopharmacology</i>, vol. 29, no. Supplement 6. Elsevier, pp. S11–S12, 2019.","ista":"Morandell J, Nicolas A, Schwarz LA, Novarino G. 2019. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 29(Supplement 6), S11–S12.","mla":"Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” <i>European Neuropsychopharmacology</i>, vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:<a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">10.1016/j.euroneuro.2019.09.040</a>.","chicago":"Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” <i>European Neuropsychopharmacology</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">https://doi.org/10.1016/j.euroneuro.2019.09.040</a>."},"title":"S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism","date_created":"2020-01-30T10:07:41Z","date_updated":"2023-09-07T14:56:17Z","issue":"Supplement 6","article_processing_charge":"No","year":"2019","intvolume":"        29","isi":1,"department":[{"_id":"GaNo"},{"_id":"LifeSc"}],"page":"S11-S12","volume":29,"quality_controlled":"1","publisher":"Elsevier","status":"public","type":"journal_article","date_published":"2019-12-13T00:00:00Z","publication_status":"published","author":[{"full_name":"Morandell, Jasmin","first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas","full_name":"Nicolas, Armel","first_name":"Armel"},{"first_name":"Lena A","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia","full_name":"Novarino, Gaia"}],"oa_version":"None","external_id":{"isi":["000502657500021"]},"day":"13","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"issn":["0924-977X"]},"month":"12"}]