7,448
Views
16
CrossRef citations to date
0
Altmetric
Research Paper

Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders

, , , , , , , , , , , , , , , & ORCID Icon show all
Pages 423-442 | Received 09 Sep 2020, Accepted 26 May 2021, Published online: 21 Jul 2021

References

  • Liang Y. Emerging concepts and functions of autophagy as a regulator of synaptic components and plasticity. Cells. 2019 Jan 9;8(1):34.
  • Vijayan V, Verstreken P. Autophagy in the presynaptic compartment in health and disease. J Cell Biol. 2017;216(7):1895–1906.
  • Hwang JY, Yan J, Zukin RS. Autophagy and synaptic plasticity: epigenetic regulation. Curr Opin Neurobiol. 2019 Dec;59:207–212.
  • Menzies FM, Fleming A, Rubinsztein DC. Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci. 2015 Jun;16(6):345–357.
  • Guo F, Liu X, Cai H, et al. Autophagy in neurodegenerative diseases: pathogenesis and therapy. Brain Pathol. 2018 Jan;28(1):3–13. .
  • Wong YC, Holzbaur ELF. Autophagosome dynamics in neurodegeneration at a glance. J Cell Sci. 2015 Apr 1;128(7):1259LP– 1267.
  • Malik BR, Maddison DC, Smith GA, et al. Autophagic and endo-lysosomal dysfunction in neurodegenerative disease. Mol Brain. 2019;12(1):100.
  • Stamatakou E, Wróbel L, Hill SM, et al. Mendelian neurodegenerative disease genes involved in autophagy. Cell Discov. 2020;6(1):24. .
  • Tang G, Gudsnuk K, Kuo SH, et al. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron. 2014 Sep 3;83(5):1131–1143.
  • Reimer RJ, Schneider K, Leal-Ortiz S, et al. Bassoon controls presynaptic autophagy through Atg5. Neuron. 2017 Feb 22;93(4):897–913.e7.
  • Shehata M, Matsumura H, Okubo-Suzuki R, et al. Neuronal stimulation induces autophagy in hippocampal neurons that is involved in AMPA receptor degradation after chemical long-term depression. J Neurosci. 2012 Jul 25;32(30):10413–10422.
  • Rowland AM, Richmond JE, Olsen JG, et al. Presynaptic terminals independently regulate synaptic clustering and autophagy of GABAA receptors in Caenorhabditis elegans. J Neurosci. 2006 Feb 8;26(6):1711–1720.
  • Artal-martinez De Narvajas A, Gomez TS, Zhang J-S, et al. Epigenetic regulation of autophagy by the methyltransferase G9a. Mol Cell Biol. 2013 Oct;33(20):3983–3993. .
  • Wei FZ, Cao Z, Wang X, et al. Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway. Autophagy. 2015;11(12):2309–2322.
  • Füllgrabe J, Lynch-Day MA, Heldring N, et al. The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy. Nature. 2013 Aug 22;500(7463):468–471.
  • Dias J, Van Nguyen N, Georgiev P, et al. Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex. Genes Dev. 2014 May 1;28(9):929–942.
  • Zollino M, Orteschi D, Murdolo M, et al. Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype. Nat Genet. 2012;44(6):636–638.
  • Koolen DA, Kramer JM, Neveling K, et al. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nat Genet. 2012;44(6):639–641.
  • Koolen DA, Pfundt R, Linda K, et al. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant. Eur J Hum Genet. 2016;24(5):652–659.
  • Meunier S, Shvedunova M, Van Nguyen N, et al. An epigenetic regulator emerges as microtubule minus-end binding and stabilizing factor in mitosis. Nat Commun. 2015;6(1):7889.
  • Chatterjee A, Seyfferth J, Lucci J, et al. MOF acetyl transferase regulates transcription and respiration in mitochondria. Cell. 2016 Oct 20;167(3):722–738.e23.
  • Arbogast T, Iacono G, Chevalier C, et al. Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition. PLoS Genet. 2017;13:7.
  • Ravens S, Fournier M, Ye T, et al. Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation. Elife. 2014 Jun;4(3):e02104.
  • Rubinsztein DC, Cuervo AM, Ravikumar B, et al. In search of an “autophagomometer”. Autophagy. 2009.5(5):585–589.
  • Klionsky DJ, Abdalla FC, Abeliovich H, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr;8(4):445–544.
  • Kabeya Y, Mizushima N, Ueno T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000 Nov;19(21):5720–5728.
  • Dooley HC, Razi M, Polson HEJ, et al. WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12. Mol Cell. 2014 Jul 17;55(2):238–252.
  • Lippai M, Lőw P. The role of the selective adaptor p62 and ubiquitin-like proteins in autophagy. Biomed Res Int. 2014 06 12;2014:832704.
  • Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010 May;221(1):3–12.
  • Klionsky DJ, Schulman BA. Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins. Nat Struct Mol Biol. 2014 Apr;21(4):336–345.
  • Rabanal-Ruiz Y, Otten EG, Korolchuk VI. mTORC1 as the main gateway to autophagy. Essays Biochem. 2017 Dec 12;61(6):565–584.
  • Jung CH, Jun CB, Ro S-H, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009 Apr;20(7):1992–2003.
  • Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011 Feb;13(2):132–141.
  • Kimura S, Noda T, Yoshimori T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy. 2007 Sep 20;3(5):452–460.
  • Leeman DS, Hebestreit K, Ruetz T, et al. Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging. Science. 2018 Mar 16;359(6381):1277LP– 1283.
  • Lipinski MM, Zheng B, Lu T, et al. Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14164–14169.
  • Lee K-M, Hwang S-K, Lee J-A. Neuronal autophagy and neurodevelopmental disorders. Exp Neurobiol. 2013 09 30;22(3):133–142.
  • Wataya-Kaneda M. Mammalian target of rapamycin and tuberous sclerosis complex. J Dermatol Sci. 2015 Aug;79(2):93–100.
  • Kim HJ, Cho MH, Shim WH, et al. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol Psychiatry. 2017 Nov;22(11):1576–1584.
  • Giordano S, Darley-Usmar V, Zhang J. Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease. Redox Biol. 2013 Dec;25(2):82–90.
  • Fujikake N, Shin M, Shimizu S. Association between autophagy and neurodegenerative diseases. Front Neurosci. 2018 May;22(12):255.
  • Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013 Aug;19(8):983–997.
  • Zhu Z, Yang C, Iyaswamy A, et al. Balancing mTOR signaling and autophagy in the treatment of Parkinson’s disease. Int J Mol Sci. 2019 Feb 8;20(3):728.
  • Valenzuela V, Nassif M, Hetz C. Unraveling the role of motoneuron autophagy in ALS. Autophagy. 2018;14(4):733–737.
  • Ramesh N, Pandey UB. Autophagy dysregulation in ALS: when protein aggregates get out of hand. Front Mol Neurosci. 2017 Aug;22(10):263.
  • Kaur SJ, McKeown SR, Rashid S. Mutant SOD1 mediated pathogenesis of amyotrophic lateral sclerosis. Gene. 2016;577(2):109–118.
  • Lieberman OJ, Sulzer D. The synaptic autophagy cycle. J Mol Biol. 2020;432(8):2589–2604.
  • Ban B-K, Jun M-H, Ryu -H-H, et al. Autophagy negatively regulates early axon growth in cortical neurons. Mol Cell Biol. 2013 08 05;33(19):3907–3919.
  • Frega M, van Gestel SHC, Linda K, et al. Rapid neuronal differentiation of induced pluripotent stem cells for measuring network activity on micro-electrode arrays. J Vis Exp. 2017:119. DOI:https://doi.org/10.3791/54900
  • Zhang Y, Pak CH, Han Y, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron. 2013;78(5):785–798.
  • Massaad CA, Klann E. Reactive oxygen species in the regulation of synaptic plasticity and memory. Antioxid Redox Signal. 2011 May 15;14(10):2013–2054.
  • Quarta E, Bravi R, Scambi I, et al. Increased anxiety-like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model. J Comp Neurol. 2015 Aug 1;523(11):1622–1638.
  • Fogarty MJ, Klenowski PM, Lee JD, et al. Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis. Sci Rep. 2016 Nov 29;6:37968.
  • Fishman I, Keown CL, Lincoln AJ, et al. Atypical cross talk between mentalizing and mirror neuron networks in autism spectrum disorder. JAMA Psychiatry. 2014 Jul;71(7):751–760.
  • Hernandez LM, Rudie JD, Green SA, et al. Neural signatures of autism spectrum disorders: insights into brain network dynamics. Neuropsychopharmacology. 2015 Jan [cited 2014 Jul 11];40(1):171–189.
  • Watanabe T, Rees G. Brain network dynamics in high-functioning individuals with autism. Nat Commun. 2017;8(1):16048.
  • Frega M, Linda K, Keller JM, et al. Neuronal network dysfunction in a model for Kleefstra syndrome mediated by enhanced NMDAR signaling. Nat Commun. 2019 Oct 30;10(1):4928.
  • Frega M, Selten M, Mossink B, et al. Distinct pathogenic genes causing intellectual disability and autism exhibit a common neuronal network hyperactivity phenotype. Cell Rep. 2020;30(1):173–186.e6.
  • Lanillos P, Oliva D, Philippsen A, et al. A review on neural network models of schizophrenia and autism spectrum disorder. Neural Networks. 2020;122:338–363.
  • Roczniak-Ferguson A, Petit CS, Froehlich F, et al. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal. 2012 Jun 12;5(228):ra42.
  • Settembre C, Zoncu R, Medina DL, et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 2012 Mar 7;31(5):1095–1108.
  • Civiletto G, Dogan SA, Cerutti R, et al. Rapamycin rescues mitochondrial myopathy via coordinated activation of autophagy and lysosomal biogenesis. EMBO Mol Med. 2018 Nov;10(11):e8799.
  • Sun Y, Zheng Y, Wang C, et al. Glutathione depletion induces ferroptosis, autophagy, and premature cell senescence in retinal pigment epithelial cells. Cell Death Dis. 2018 Jul 9;9(7):753.
  • Crino PB. The mTOR signalling cascade: paving new roads to cure neurological disease. Nat Rev Neurol. 2016 Jul;12(7):379–392.
  • Yu L, McPhee CK, Zheng L, et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010 Jun 17;465(7300):942–946.
  • Settembre C, Di MC, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011 Jun 17;332(6036):1429–1433.
  • Napolitano G, Esposito A, Choi H, et al. mTOR-dependent phosphorylation controls TFEB nuclear export. Nat Commun. 2018 Aug 17;9(1):3312.
  • Brown RA, Voit A, Srikanth MP, et al. MTOR hyperactivity mediates lysosomal dysfunction in Gaucher’s disease iPSC-neuronal cells. Dis Model Mech. 2019 Oct 16;12(10):dmm038596.
  • Li L, Tan J, Miao Y, et al. ROS and autophagy: interactions and molecular regulatory mechanisms. Cell Mol Neurobiol. 2015;35(5):615–621.
  • Li M, Zhao L, Liu J, et al. Multi-mechanisms are involved in reactive oxygen species regulation of mTORC1 signaling. Cell Signal. 2010 Oct;22(10):1469–1476.
  • Yalcin S, Marinkovic D, Mungamuri SK, et al. ROS-mediated amplification of AKT/mTOR signalling pathway leads to myeloproliferative syndrome in Foxo3−/− mice. EMBO J. 2010 Dec 15;29(24):4118–4131.
  • Kim J-H, Choi TG, Park S, et al. Mitochondrial ROS-derived PTEN oxidation activates PI3K pathway for mTOR-induced myogenic autophagy. Cell Death Differ. 2018 Nov;25(11):1921–1937.
  • Zhang J, Kim J, Alexander A, et al. A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS. Nat Cell Biol. 2013;15(10):1186–1196.
  • Wang X, Fu Y-F, Liu X, et al. ROS promote Ox-LDL-induced platelet activation by up-regulating autophagy through the inhibition of the PI3K/AKT/mTOR pathway. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2018;50(5):1779–1793.
  • Zhang X, Cheng X, Yu L, et al. MCOLN1 is a ROS sensor in lysosomes that regulates autophagy. Nat Commun. 2016 Jun;7:12109.
  • Chang D, Nalls MA, Hallgrímsdóttir IB, et al. A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat Genet. 2017 Oct;49(10):1511–1516.
  • Beal MF. Mitochondrial dysfunction and oxidative damage in Alzheimer’s and Parkinson’s diseases and coenzyme Q 10 as a potential treatment. J Bioenerg Biomembr. 2004 Aug;36(4):381–386.
  • Dias V, Junn E, Mouradian MM. The role of oxidative stress in parkinson’s disease. J Parkinsons Dis. 2013;3(4):461–491.
  • Wei Z, Li X, Li X, et al. Oxidative stress in Parkinson’s disease: a systematic review and meta-analysis. Front Mol Neurosci. 2018 Jul;5(11):236.
  • Sedlackova L, Kelly G, Korolchuk VI. The pROS of autophagy in neuronal health. J Mol Biol. 2020 Apr 3;432(8):2546–2559.
  • Beckhauser TF, Francis-Oliveira J, De Pasquale R. Reactive oxygen species: physiological and physiopathological effects on synaptic plasticity. J Exp Neurosci. 2016 Sep 4;10(Suppl 1):23–48.
  • Klann E. Cell-permeable scavengers of superoxide prevent long-term potentiation in hippocampal area CA1. J Neurophysiol. 1998 Jul;80(1):452–457.
  • Thiels E, Urban NN, Gonzalez-Burgos GR, et al. Impairment of long-term potentiation and associative memory in mice that overexpress extracellular superoxide dismutase. J Neurosci. 2000 Oct 15;20(20):7631–7639.
  • Knapp LT, Klann E. Potentiation of hippocampal synaptic transmission by superoxide requires the oxidative activation of protein kinase C. J Neurosci. 2002 Feb 1;22(3):674–683.
  • Hu D, Serrano F, Oury TD, et al. Aging-dependent alterations in synaptic pl7asticity and memory in mice that overexpress extracellular superoxide dismutase. J Neurosci. 2006 Apr 12;26(15):3933–3941.
  • Keen C, Samango-Sprouse C, Dubbs H, et al. 10-year-old female with intragenic KANSL1 mutation, no KANSL1-related intellectual disability, and preserved verbal intelligence. Am J Med Genet A. 2017 Mar;173(3):762–765. .
  • Maley AM, Spraker MK, De Vries BBA, et al. Vitiligo in the Koolen-de Vries or 17q21.31 microdeletion syndrome. Clin Dysmorphol. 2015 Apr;24(2):86–87. .
  • Ran FA, Hsu PD, Wright J, et al. Genome engineering using the CRISPR-Cas9 system. Nat Protoc. 2013;8(11):2281–2308. .
  • Rodenburg RJT. Biochemical diagnosis of mitochondrial disorders. J Inherit Metab Dis. 2011 Apr;34(2):283–292.
  • Srere PABT-M. Citrate synthase: [EC 4.1.3.7. Citrate oxaloacetate-lyase (CoA-acetylating)]. Methods in enzymology 1969;. 3:3–11.
  • Klein Gunnewiek TM, Van Hugte EJH, Frega M, et al. m.3243A > G-induced mitochondrial dysfunction impairs human neuronal development and reduces neuronal network activity and synchronicity. Cell Rep. 2020;31(3):107538.
  • Da SHOLL. Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat. 1953 Oct;87(4):387–406.