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The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc

Molecular Psychiatry volume 26, pages 1980–1995 (2021)Cite this article

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Abstract

Kaufman oculocerebrofacial syndrome (KOS) is a severe autosomal recessive disorder characterized by intellectual disability, developmental delays, microcephaly, and characteristic dysmorphisms. Biallelic mutations of UBE3B, encoding for a ubiquitin ligase E3B are causative for KOS. In this report, we characterize neuronal functions of its murine ortholog Ube3b and show that Ube3b regulates dendritic branching in a cell-autonomous manner. Moreover, Ube3b knockout (KO) neurons exhibit increased density and aberrant morphology of dendritic spines, altered synaptic physiology, and changes in hippocampal circuit activity. Dorsal forebrain-specific Ube3b KO animals show impaired spatial learning, altered social interactions, and repetitive behaviors. We further demonstrate that Ube3b ubiquitinates the catalytic γ-subunit of calcineurin, Ppp3cc, the overexpression of which phenocopies Ube3b loss with regard to dendritic spine density. This work provides insights into the molecular pathologies underlying intellectual disability-like phenotypes in a genetically engineered mouse model.

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Fig. 1: Ube3b is expressed in developing and mature murine central nervous system and associates with postsynaptic densities.
Fig. 2: Ube3b loss in neurons leads to dramatic impairment of neurite branching.
Fig. 3: Ube3b deletion in neurons induces morphological aberrances in dendritic spines in vivo.
Fig. 4: Synaptic transmission is altered in Ube3b cKO autaptic neurons.
Fig. 5: Ube3b cKO male mice show loss of spatial memory and increased sociability.
Fig. 6: Proteomic screen identifies Ppp3cc as a Ube3b substrate.

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References

  1. Tønnesen J, Nägerl UV. Dendritic spines as tunable regulators of synaptic signals. Front Psychiatry. 2016;7:101.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ambrozkiewicz MC, Kawabe H. HECT-type E3 ubiquitin ligases in nerve cell development and synapse physiology. FEBS Lett. 2015;589:1635–43.

    Article  CAS  PubMed  Google Scholar 

  3. Kawabe H, Brose N. The role of ubiquitylation in nerve cell development. Nat Rev Neurosci. 2011;12:251–68.

    Article  CAS  PubMed  Google Scholar 

  4. Hershko A, Heller H, Elias S, Ciechanover A. Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem. 1983;258:8206–14.

    Article  CAS  PubMed  Google Scholar 

  5. Kaiser SE, Riley BE, Shaler TA, Trevino RS, Becker CH, Schulman H, et al. Protein standard absolute quantification (PSAQ) method for the measurement of cellular ubiquitin pools. Nat Methods. 2011;8:691–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hicke L, Riezman H. Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell. 1996;84:277–87.

    Article  CAS  PubMed  Google Scholar 

  7. Rotin D, Kumar S. Physiological functions of the HECT family of ubiquitin ligases. Nat Rev Mol Cell Biol. 2009;10:398–409.

    Article  CAS  PubMed  Google Scholar 

  8. Huibregtse JM, Scheffner M, Beaudenon S, Howley PM. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci USA. 1995;92:2563–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ambrozkiewicz MC, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, et al. Polarity acquisition in cortical neurons is driven by synergistic action of Sox9-regulated Wwp1 and Wwp2 E3 ubiquitin ligases and intronic miR-140. Neuron. 2018;100:1097–1115.e15.

    Article  CAS  PubMed  Google Scholar 

  10. Hsia H-E, Kumar R, Luca R, Takeda M, Courchet J, Nakashima J, et al. Ubiquitin E3 ligase Nedd4-1 acts as a downstream target of PI3K/PTEN-mTORC1 signaling to promote neurite growth. Proc Natl Acad Sci USA. 2014;111:13205–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kawabe H, Neeb A, Dimova K, Young SM, Takeda M, Katsurabayashi S, et al. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010;65:358–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Basel-Vanagaite L, Dallapiccola B, Ramirez-Solis R, Segref A, Thiele H, Edwards A, et al. Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome. Am J Hum Genet. 2012;91:998–1010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Basel-Vanagaite L, Yilmaz R, Tang S, Reuter MS, Rahner N, Grange DK, et al. Expanding the clinical and mutational spectrum of Kaufman oculocerebrofacial syndrome with biallelic UBE3B mutations. Hum Genet. 2014;133:939–49.

    Article  CAS  PubMed  Google Scholar 

  14. Flex E, Ciolfi A, Caputo V, Fodale V, Leoni C, Melis D, et al. Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome. J Med Genet. 2013;50:493–9.

    Article  CAS  PubMed  Google Scholar 

  15. Pedurupillay CRJ, Barøy T, Holmgren A, Blomhoff A, Vigeland MD, Sheng Y, et al. Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B. Am J Med Genet A. 2015;167A:657–63.

    Article  PubMed  CAS  Google Scholar 

  16. Chahrour MH, Yu TW, Lim ET, Ataman B, Coulter ME, Hill RS, et al. Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genet. 2012;8:e1002635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Svilar D, Dyavaiah M, Brown AR, Tang J, Li J, McDonald PR, et al. Alkylation sensitivity screens reveal a conserved cross-species functionome. Mol Cancer Res MCR. 2012;10:1580–96.

    Article  CAS  PubMed  Google Scholar 

  18. Braganza A, Li J, Zeng X, Yates NA, Dey NB, Andrews J, et al. UBE3B is a calmodulin-regulated, mitochondrion-associated E3 Ubiquitin Ligase. J Biol Chem. 2017;292:2470–84.

    Article  CAS  PubMed  Google Scholar 

  19. Cheon S, Kaur K, Nijem N, Tuncay IO, Kumar P, Dean M, et al. The ubiquitin ligase UBE3B, disrupted in intellectual disability and absent speech, regulates metabolic pathways by targeting BCKDK. Proc Natl Acad Sci. 2019;116:3662–7. https://doi.org/10.1073/pnas.1818751116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JLR, Jones KR. Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci J Soc Neurosci. 2002;22:6309–14.

    Article  CAS  Google Scholar 

  21. Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, et al. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci USA. 1996;93:5860–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Thomas KR, Capecchi MR. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell. 1987;51:503–12.

    Article  CAS  PubMed  Google Scholar 

  23. Koch S, Mueller S, Foddis M, Bienert T, von Elverfeldt D, Knab F, et al. Atlas registration for edema-corrected MRI lesion volume in mouse stroke models. J Cereb Blood Flow Metab. 2019;39:313–23.

    Article  PubMed  Google Scholar 

  24. Zaqout S, Kaindl AM. Golgi–Cox staining step by step. Front Neuroanat. 2016;10:38.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Dere E, Dahm L, Lu D, Hammerschmidt K, Ju A, Tantra M, et al. Heterozygous ambra1 deficiency in mice: a genetic trait with autism-like behavior restricted to the female gender. Front Behav Neurosci. 2014;8:181.

    PubMed  PubMed Central  Google Scholar 

  26. Netrakanti PR, Cooper BH, Dere E, Poggi G, Winkler D, Brose N, et al. Fast cerebellar reflex circuitry requires synaptic vesicle priming by munc13-3. Cerebellum Lond Engl. 2015;14:264–83.

    Article  CAS  Google Scholar 

  27. Telley L, Agirman G, Prados J, Amberg N, Fièvre S, Oberst P, et al. Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex. Science. 2019;364. pii: eaav2522. https://doi.org/10.1126/science.aav2522.

    Article  CAS  Google Scholar 

  28. Song JY, Ichtchenko K, Südhof TC, Brose N. Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci USA. 1999;96:1100–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Coley AA, Gao W-J. PSD95: A synaptic protein implicated in schizophrenia or autism? Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:187–94.

    Article  CAS  PubMed  Google Scholar 

  30. Nakanishi M, Nomura J, Ji X, Tamada K, Arai T, Takahashi E, et al. Functional significance of rare neuroligin 1 variants found in autism. PLoS Genet. 2017;13:e1006940.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Wang Q, Moore MJ, Adelmant G, Marto JA, Silver PA. PQBP1, a factor linked to intellectual disability, affects alternative splicing associated with neurite outgrowth. Genes Dev. 2013;27:615–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Guo H, Hong S, Jin XL, Chen RS, Avasthi PP, Tu YT, et al. Specificity and efficiency of Cre-mediated recombination in Emx1-Cre knock-in mice. Biochem Biophys Res Commun. 2000;273:661–5.

    Article  CAS  PubMed  Google Scholar 

  33. Koleske AJ. Molecular mechanisms of dendrite stability. Nat Rev Neurosci. 2013;14:536–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rosário M, Schuster S, Jüttner R, Parthasarathy S, Tarabykin V, Birchmeier W. Neocortical dendritic complexity is controlled during development by NOMA-GAP-dependent inhibition of Cdc42 and activation of cofilin. Genes Dev. 2012;26:1743–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Dindot SV, Antalffy BA, Bhattacharjee MB, Beaudet AL. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum Mol Genet. 2008;17:111–8.

    Article  CAS  PubMed  Google Scholar 

  36. Saito T. In vivo electroporation in the embryonic mouse central nervous system. Nat Protoc. 2006;1:1552–8.

    Article  CAS  PubMed  Google Scholar 

  37. Bekkers JM, Stevens CF. Excitatory and inhibitory autaptic currents in isolated hippocampal neurons maintained in cell culture. Proc Natl Acad Sci USA. 1991;88:7834–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ripamonti S, Ambrozkiewicz MC, Guzzi F, Gravati M, Biella G, Bormuth I, et al. Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons. ELife. 2017;6. pii: e22466. https://doi.org/10.7554/eLife.22466.

    Article  Google Scholar 

  39. Chau V, Tobias JW, Bachmair A, Marriott D, Ecker DJ, Gonda DK, et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science. 1989;243:1576–83.

    Article  CAS  PubMed  Google Scholar 

  40. Duncan LM, Piper S, Dodd RB, Saville MK, Sanderson CM, Luzio JP, et al. Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules. EMBO J. 2006;25:1635–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Grice GL, Nathan JA. The recognition of ubiquitinated proteins by the proteasome. Cell Mol Life Sci CMLS. 2016;73:3497–506.

    Article  CAS  PubMed  Google Scholar 

  42. Gong TW, Hegeman AD, Shin JJ, Adler HJ, Raphael Y, Lomax MI. Identification of genes expressed after noise exposure in the chick basilar papilla. Hear Res. 1996;96:20–32.

    Article  CAS  PubMed  Google Scholar 

  43. Mazumder MK, Paul R, Bhattacharya P, Borah A. Neurological sequel of chronic kidney disease: from diminished Acetylcholinesterase activity to mitochondrial dysfunctions, oxidative stress and inflammation in mice brain. Sci Rep. 2019;9:3097.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Vanholder R, De Smet R, Glorieux G, Argilés A, Baurmeister U, Brunet P, et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003;63:1934–43.

    Article  CAS  PubMed  Google Scholar 

  45. Ramakers GJ. Rho proteins and the cellular mechanisms of mental retardation. Am J Med Genet. 2000;94:367–71.

    Article  CAS  PubMed  Google Scholar 

  46. Dierssen M, Ramakers GJA. Dendritic pathology in mental retardation: from molecular genetics to neurobiology. Genes Brain Behav. 2006;5:48–60.

    Article  CAS  PubMed  Google Scholar 

  47. Engert F, Bonhoeffer T. Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 1999;399:66–70.

    Article  CAS  PubMed  Google Scholar 

  48. Noguchi J, Matsuzaki M, Ellis-Davies GCR, Kasai H. Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites. Neuron 2005;46:609–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Verma V, Paul A, Amrapali Vishwanath A, Vaidya B, Clement JP. Understanding intellectual disability and autism spectrum disorders from common mouse models: synapses to behaviour. Open Biol. 2019;9:180265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA, Weiler IJ, et al. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci. 1997;94:5401–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Csicsvari J, Jamieson B, Wise KD, Buzsáki G. Mechanisms of gamma oscillations in the hippocampus of the behaving rat. Neuron. 2003;37:311–22.

    Article  CAS  PubMed  Google Scholar 

  52. Hitti FL, Siegelbaum SA. The hippocampal CA2 region is essential for social memory. Nature. 2014;508:88–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Silverman JL, Yang M, Lord C, Crawley JN. Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci. 2010;11:490–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yilmaz R, Szakszon K, Altmann A, Altunoglu U, Senturk L, McGuire M, et al. Kaufman oculocerebrofacial syndrome: novel UBE3B mutations and clinical features in four unrelated patients. Am J Med Genet A. 2018;176:187–93.

    Article  CAS  PubMed  Google Scholar 

  55. American Psychiatric Association. diagnostic and statistical manual of mental disorders. 5th ed. American Psychiatric Association; 2013. https://www.psychiatry.org/psychiatrists/practice/dsm.

  56. Sutton LP, Orlandi C, Song C, Oh WC, Muntean BS, Xie K, et al. Orphan receptor GPR158 controls stress-induced depression. ELife. 2018;7. pii: e33273. https://doi.org/10.7554/eLife.33273.

    Article  Google Scholar 

  57. van Diepen MT, Parsons M, Downes CP, Leslie NR, Hindges R, Eickholt BJ. MyosinV controls PTEN function and neuronal cell size. Nat Cell Biol. 2009;11:1191–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Konietzny A, González-Gallego J, Bär J, Perez-Alvarez A, Drakew A, Demmers JAA, et al. Myosin V regulates synaptopodin clustering and localization in the dendrites of hippocampal neurons. J Cell Sci. 2019;132. pii: jcs230177. https://doi.org/10.1242/jcs.230177.

    Article  CAS  Google Scholar 

  59. Belvindrah R, Natarajan K, Shabajee P, Bruel-Jungerman E, Bernard J, Goutierre M, et al. Mutation of the α-tubulin Tuba1a leads to straighter microtubules and perturbs neuronal migration. J Cell Biol. 2017;216:2443–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chandran V, Coppola G, Nawabi H, Omura T, Versano R, Huebner EA, et al. A systems-level analysis of the peripheral nerve intrinsic axonal growth program. Neuron. 2016;89:956–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Li M, Wen H, Yan Z, Ding T, Long L, Qin H, et al. Temporal-spatial expression of ENOLASE after acute spinal cord injury in adult rats. Neurosci Res. 2014;79:76–82.

    Article  CAS  PubMed  Google Scholar 

  62. Lin L, Sun W, Kung F, Dell’Acqua ML, Hoffman DA. AKAP79/150 impacts intrinsic excitability of hippocampal neurons through phospho-regulation of A-type K+ channel trafficking. J Neurosci J Soc Neurosci. 2011;31:1323–32.

    Article  CAS  Google Scholar 

  63. Alagarsamy S, Saugstad J, Warren L, Mansuy IM, Gereau RW, Conn PJ. NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin. Neuropharmacology. 2005;49:135–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Horiuchi Y, Ishiguro H, Koga M, Inada T, Iwata N, Ozaki N, et al. Support for association of the PPP3CC gene with schizophrenia. Mol Psychiatry. 2007;12:891–3.

    Article  CAS  PubMed  Google Scholar 

  65. Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, et al. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci. 2003;100:8987–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the German Research Foundation (SPP1365/KA3423/1-1 and KA3423/3-1, HK; DFG TA 303/4-2, VT), and the Russian Scientific Foundation (19-14-00345, VT), JSPS KAKENHI Grant Numbers 15K21769 (HK), The Mother and Child Health Foundation (HK), the Uehara Memorial Foundation (HK), and the Fritz Thyssen Foundation (HK). Funding to SM and PBS was provided by the German Federal Ministry of Education and Research (BMBF, Center for Stroke Research Berlin 01EO1301), the BMBF under the ERA-NET NEURON scheme (01EW1811), and the German Research Foundation (DFG, Project 428869206 and EXC NeuroCure). We would like to acknowledge Nils Brose for his help with project administration and insightful remarks regarding the conceptualization. We thank Fritz Benseler, Klaus-Peter Hellman, Bernd Hesse-Niessen, Ivonne Thanhäuser, Dayana Warnecke, Christiane Harenberg, Maik Schlieper, Dörte Hesse, Stefan Paul Koch, Jutta Schüler, Olaf Ninnemann, Claudia Pallasch, Rike Dannenberg, and Denis Lajkó and animal facilities of Max Planck Institute of Experimental Medicine and of Charité University Hospital. We acknowledge Alex Knebel, Thimo Kurz, Carlos Henrique Vieira e Vieira, Matthias Selbach, Hannelore Ehrenreich, Ahmed Mansouri, and Judith Stegmüller for their feedback.

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  1. These authors contributed equally: Victor Tarabykin, Hiroshi Kawabe

Authors and Affiliations

  1. Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany

    Mateusz C. Ambrozkiewicz, Manuela Schwark, Silvia Ripamonti, Hong Jun Rhee, Bekir Altas, JeongSeop Rhee & Hiroshi Kawabe

  2. International Max Planck Research School for Neurosciences, Georg-August-Universität Göttingen, Griesebachstr. 5, 37077, Göttingen, Germany

    Mateusz C. Ambrozkiewicz & Bekir Altas

  3. Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany

    Mateusz C. Ambrozkiewicz, Theres Schaub, Alina Smorodchenko, A. Ioana Weber, Stephen T. Horan, Marta Rosário & Victor Tarabykin

  4. Institute of Neuroscience, Lobachevsky University of Nizhny Novgorod, pr. Gagarina 24, Nizhny Novgorod, Russian Federation

    Ekaterina Borisova & Victor Tarabykin

  5. Center for Rare Diseases (ZSE Ulm), Ulm University Hospital, Eythstraße 24, 89075, Ulm, Germany

    Rüstem Yilmaz & Guntram Borck

  6. Department of Experimental Neurology and Center for Stroke Research, Charité—Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Susanne Mueller & Philipp Boehm-Sturm

  7. NeuroCure Cluster of Excellence and Charité Core Facility 7T Experimental MRIs, Charité—Universitätsmedizin Berlin, Berlin, Germany

    Susanne Mueller & Philipp Boehm-Sturm

  8. Proteomics Group, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany

    Lars Piepkorn & Olaf Jahn

  9. Institute of Child Neurology, Schneider’s Children Medical Center, Petah Tikvah, Israel

    Rachel Straussberg

  10. Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Rachel Straussberg

  11. Basic Medical Science Department, College of Medicine, QU Health, Qatar University, Doha, Qatar

    Sami Zaqout

  12. Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany

    Ekrem Dere

  13. Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Katrin I. Willig

  14. Max Planck Institute of Experimental Medicine, Göttingen, Germany

    Katrin I. Willig

  15. Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Hiroshi Kawabe

  16. Department of Gerontology, Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, 2-2 Minatojima-minamimachi Chuo-ku, Kobe, 650-0047, Japan

    Hiroshi Kawabe

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Ambrozkiewicz, M.C., Borisova, E., Schwark, M. et al. The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc. Mol Psychiatry 26, 1980–1995 (2021). https://doi.org/10.1038/s41380-020-0714-8

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