The stress-induced Atf3-gelsolin cascade underlies dendritic spine deficits in neuronal models of tuberous sclerosis complex

Journal of Neuroscience

Volumn 35, Issue 30, 2015, Pages 10762-10772

  Nie, Duyu ^a,d   Chen, Zehua ^b   Ebrahimi Fakhari, Darius ^a   Di Nardo, Alessia ^a   Julich, Kristina ^a   Robson, Victoria K ^a   Cheng, Yung Chih ^a   Woolf, Clifford J ^a   Heiman, Myriam ^b,c   Sahin, Mustafa ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^d TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autism; Dendiritic spines; mTOR; Protein synthesis; Translation

Indexed keywords

ACTIN; ACTIVATING TRANSCRIPTION FACTOR 3; GELSOLIN; MESSENGER RNA; PUROMYCIN; RAPAMYCIN; SHORT HAIRPIN RNA; UNCOUPLING PROTEIN 2; SMALL INTERFERING RNA; TARGET OF RAPAMYCIN KINASE; TRANSCRIPTOME;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CBLN1 GENE; CONTROLLED STUDY; DENDRITIC SPINE; EMBRYO; FEMALE; GENE; GENETIC TRANSFECTION; IMMUNOCYTOCHEMISTRY; LENTIVIRUS INFECTION; MALE; MICROARRAY ANALYSIS; MOUSE; NERVE CELL CULTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; RAT; REAL TIME POLYMERASE CHAIN REACTION; RNA EXTRACTION; SNAP91 GENE; SPINE MALFORMATION; STRESS; TELOMERIC REPEAT AMPLIFICATION PROTOCOL; TUBEROUS SCLEROSIS; WESTERN BLOTTING; ANIMAL; DISEASE MODEL; DNA MICROARRAY; GENETICS; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; METABOLISM; MUTANT MOUSE STRAIN; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ACTIVATING TRANSCRIPTION FACTOR 3; ANIMALS; BLOTTING, WESTERN; DENDRITIC SPINES; DISEASE MODELS, ANIMAL; FEMALE; GELSOLIN; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; MALE; MICE; MICE, MUTANT STRAINS; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; RATS; REAL-TIME POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TRANSCRIPTOME; TRANSFECTION; TUBEROUS SCLEROSIS;

EID: 84938520393     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4796-14.2015     Document Type: Article

References (55)

1. Asato MR, Hardan AY (2004) Neuropsychiatric problems in tuberous sclerosis complex. J Child Neurol 19:241-249. CrossRef Medline
2. Auerbach BD, Osterweil EK, Bear MF (2011) Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 480:63- 68. CrossRef Medline
3. Bateup HS, Takasaki KT, Saulnier JL, Denefrio CL, Sabatini BL (2011) Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. J Neurosci 31:8862- 8869. CrossRef Medline
4. Bateup HS, Johnson CA, Denefrio CL, Saulnier JL, Kornacker K, Sabatini BL (2013) Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis. Neuron 78: 510-522. CrossRef Medline
5. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57:289 -300.
6. Chauhan A, Chauhan V (2006) Oxidative stress in autism. Pathophysiology 13:171-181. CrossRef Medline
7. Choi YJ, Di Nardo A, Kramvis I, Meikle L, Kwiatkowski DJ, Sahin M, He X (2008) Tuberous sclerosis complex proteins control axon formation. Genes Dev 22:2485-2495. CrossRef Medline
8. Chuang YC, Lin TK, Huang HY, Chang WN, Liou CW, Chen SD, Chang AY, Chan SH (2012) Peroxisome proliferator-activated receptors gamma/ mitochondrial uncoupling protein 2 signaling protects against seizureinduced neuronal cell death in the hippocampus following experimental status epilepticus. J Neuroinflammation 9:184. CrossRef Medline
9. Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA (2010) The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 51:1236 -1241. CrossRef Medline
10. Di Mario FJ Jr, Sahin M, Ebrahimi-Fakhari D (2015) Tuberous sclerosis complex. Pediatr Clin North Am 62:633- 648. CrossRef Medline
11. DiNardo A, Kramvis I, Cho N, Sadowski A, Meikle L, Kwiatkowski DJ, Sahin M (2009) Tuberous sclerosis complex activity is required to control neuronal stress responses in an mTOR-dependent manner. J Neurosci 29:5926 -5937. CrossRef Medline
12. Doyle JP, Dougherty JD, Heiman M, Schmidt EF, Stevens TR, Ma G, Bupp S, Shrestha P, Shah RD, Doughty ML, Gong S, Greengard P, Heintz N (2008) Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell 135:749 -762. CrossRef Medline
13. Ebrahimi-Fakhari D, Sahin M (2015) Autism and the synapse: emerging mechanisms and mechanism-based therapies. Curr Opin Neurol 28: 91-102. CrossRef Medline
14. Feliciano DM, Lin TV, Hartman NW, Bartley CM, Kubera C, Hsieh L, Lafourcade C, O'Keefe RA, Bordey A (2013) A circuitry and biochemical basis for tuberous sclerosis symptoms: from epilepsy to neurocognitive deficits. Int J Dev Neurosci 31:667- 678. CrossRef Medline
15. Furukawa K, Fu W, Li Y, Witke W, Kwiatkowski DJ, Mattson MP (1997) The actin-severing protein gelsolin modulates calcium channel and NMDA receptor activities and vulnerability to excitotoxicity in hippocampal neurons. J Neurosci 17:8178-8186. Medline
16. Gkogkas CG, Khoutorsky A, Ran I, Rampakakis E, Nevarko T, Weatherill DB, Vasuta C, Yee S, Truitt M, Dallaire P, Major F, Lasko P, Ruggero D, Nader K, Lacaille JC, Sonenberg N (2013) Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 493:371-377. CrossRef Medline
17. Harms C, Bösel J, Lautenschlager M, Harms U, Braun JS, Hörtnagl H, Dirnagl U, Kwiatkowski DJ, Fink K, Endres M (2004) Neuronal gelsolin prevents apoptosis by enhancing actin depolymerization. Mol Cell Neurosci 25:69-82. CrossRef Medline
18. Hashimoto Y, Zhang C, Kawauchi J, Imoto I, Adachi MT, Inazawa J, Amagasa T, Hai T, Kitajima S (2002) An alternatively spliced isoform of transcriptional repressor ATF3 and its induction by stress stimuli. Nucleic Acids Res 30:2398 -2406. CrossRef Medline
19. Heiman M, Schaefer A, Gong S, Peterson JD, Day M, Ramsey KE, Suárez- Farinas M, Schwarz C, Stephan DA, Surmeier DJ, Greengard P, Heintz N (2008) A translational profiling approach for the molecular characterization of CNS cell types. Cell 135:738 -748. CrossRef Medline
20. Heiman M, Kulicke R, Fenster RJ, Greengard P, Heintz N (2014) Cell typespecific mRNA purification by translating ribosome affinity purification (TRAP). Nat Protoc 9:1282-1291. CrossRef Medline
21. Hunt D, Raivich G, Anderson PN (2012) Activating transcription factor 3 and the nervous system. Front Mol Neurosci 5:7. CrossRef Medline
22. Ito-Ishida A, Miyazaki T, Miura E, Matsuda K, Watanabe M, Yuzaki M, Okabe S (2012) Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation. Neuron 76:549 -564. CrossRef Medline
23. Jeste SS, Sahin M, Bolton P, Ploubidis GB, Humphrey A (2008) Characterization of autism in young children with tuberous sclerosis complex. J Child Neurol 23:520 -525. CrossRef Medline
24. Kim-Han JS, Dugan LL (2005) Mitochondrial uncoupling proteins in the central nervous system. Antioxid Redox Signal 7:1173-1181. CrossRef Medline
25. Knight ZA, Tan K, Birsoy K, Schmidt S, Garrison JL, Wysocki RW, Emiliano A, Ekstrand MI, Friedman JM (2012) Molecular profiling of activated neurons by phosphorylated ribosome capture. Cell 151:1126 -1137. CrossRef Medline
26. Lipton JO, Sahin M (2014) The neurology of mTOR. Neuron 84:275-291. CrossRef Medline
27. Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, Guastella AJ (2015) Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20:440-446. CrossRef Medline
28. Matsuda K, YuzakiM (2011) Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. Eur J Neurosci 33:1447-1461. CrossRef Medline
29. Meikle L, Talos DM, Onda H, Pollizzi K, Rotenberg A, Sahin M, Jensen FE, Kwiatkowski DJ (2007) A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival. J Neurosci 27:5546 -5558. CrossRef Medline
30. Minshew NJ, Goldstein G, Dombrowski SM, Panchalingam K, Pettegrew JW (1993) A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes. Biol Psychiatry 33:762-773. CrossRef Medline
31. Morris SA, Schröder S, Plessmann U, Weber K, Ungewickell E (1993) Clathrin assembly protein AP180: primary structure, domain organization and identification of a clathrin binding site. EMBO J 12:667- 675. Medline
32. Nie D, SahinM (2012) A genetic model to dissect the role of Tsc-mTORC1 in neuronal cultures. Methods Mol Biol 821:393- 405. CrossRef Medline
33. Nie D, Di Nardo A, Han JM, Baharanyi H, Kramvis I, Huynh T, Dabora S, Codeluppi S, Pandolfi PP, Pasquale EB, SahinM (2010) Tsc2-Rheb signaling regulates EphA-mediated axon guidance. Nat Neurosci 13: 163-172. CrossRef Medline
34. Onda H, Lueck A, Marks PW, Warren HB, Kwiatkowski DJ (1999) Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest 104:687- 695. CrossRef Medline
35. Petralia RS, Wang YX, Indig FE, Bushlin I,WuF, Mattson MP, Yao PJ (2013) Reduction of AP180 and CALM produces defects in synaptic vesicle size and density. Neuromol Med 15:49-60. CrossRef Medline
36. Robinson MD, Oshlack A (2010) A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol 11:R25. CrossRef Medline
37. Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139 -140. CrossRef Medline
38. Rossignol DA, Frye RE (2014) Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol 5:150. CrossRef Medline
39. Santini E, Huynh TN, MacAskill AF, Carter AG, Pierre P, Ruggero D, Kaphzan H, Klann E (2013) Exaggerated translation causes synaptic and behavioural aberrations associated with autism. Nature 493:411- 415. CrossRef Medline
40. Sanz E, Yang L, Su T, Morris DR, McKnight GS, Amieux PS (2009) Celltype- specific isolation of ribosome-associated mRNA from complex tissues. Proc Natl Acad Sci U S A 106:13939 -13944. CrossRef Medline
41. Seijffers R, Mills CD, Woolf CJ (2007) ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration. J Neurosci 27:7911-7920. CrossRef Medline
42. Seijffers R, Zhang J, Matthews JC, Chen A, Tamrazian E, Babaniyi O, Selig M, Hynynen M, Woolf CJ, Brown RH Jr (2014) ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation. Proc Natl Acad Sci U S A 111: 1622-1627. CrossRef Medline
43. Sugiura H, Yasuda S, Katsurabayashi S, Kawano H, Endo K, Takasaki K, Iwasaki K, Ichikawa M, Kobayashi T, Hino O, Yamagata K (2015) Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex. Nat Commun 6:6842. CrossRef Medline
44. Tavazoie SF, Alvarez VA, Ridenour DA, Kwiatkowski DJ, Sabatini BL (2005) Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2. Nat Neurosci 8:1727-1734. CrossRef Medline
45. Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM (2012) A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485:109 -113. CrossRef Medline
46. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, Steinberg J, Crawley JN, Regehr WG, SahinM (2012) Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 488: 647-651. CrossRef Medline
47. Tsujino H, Kondo E, Fukuoka T, Dai Y, Tokunaga A, Miki K, Yonenobu K, Ochi T, Noguchi K (2000) Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: a novel neuronal marker of nerve injury. Mol Cell Neurosci 15:170 -182. CrossRef Medline
48. Wang Q, Mora-Jensen H, Weniger MA, Perez-Galan P, Wolford C, Hai T, Ron D, Chen W, Trenkle W, Wiestner A, Ye Y (2009) ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells. Proc Natl Acad Sci U S A 106:2200 -2205. CrossRef Medline
49. Wu F, Mattson MP, Yao PJ (2010) Neuronal activity and the expression of clathrin-assembly protein AP180. Biochem Biophys Res Commun 402: 297-300. CrossRef Medline
50. Yao PJ, Coleman PD, Calkins DJ (2002) High-resolution localization of clathrin assembly protein AP180 in the presynaptic terminals of mammalian neurons. J Comp Neurol 447:152-162. CrossRef Medline
51. Yasuda S, Sugiura H, Katsurabayashi S, Shimada T, Tanaka H, Takasaki K, Iwasaki K, Kobayashi T, Hino O, Yamagata K (2014) Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex. Sci Rep 4:5155. CrossRef Medline
52. Yuan X, Yu L, Li J, Xie G, Rong T, Zhang L, Chen J, Meng Q, Irving AT, Wang D, Williams ED, Liu JP, Sadler AJ, Williams BR, Shen L, Xu D (2013) ATF3 suppresses metastasis of bladder cancer by regulating gelsolinmediated remodeling of the actin cytoskeleton. Cancer Res 73:3625-3637. CrossRef Medline
53. Zhang L, Bartley CM, Gong X, Hsieh LS, Lin TV, Feliciano DM, Bordey A (2014) MEK-ERK1/2-dependent FLNA overexpression promotes abnormal dendritic patterning in tuberous sclerosis independent of mTOR. Neuron 84:78 -91. CrossRef Medline
54. Zhang SJ, Zou M, Lu L, Lau D, Ditzel DA, Delucinge-Vivier C, Aso Y, Descombes P, Bading H (2009) Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity. PLoS Genet 5:e1000604. CrossRef Medline
55. Zhang SJ, Buchthal B, Lau D, Hayer S, Dick O, Schwaninger M, Veltkamp R, Zou M, Weiss U, Bading H (2011) A signaling cascade of nuclear calcium-CREB-ATF3 activated by synaptic NMDA receptors defines a gene repression module that protects against extrasynaptic NMDA receptor-induced neuronal cell death and ischemic brain damage. J Neurosci 31:4978-4990. CrossRef Medline