The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Autism-related deficits via dysregulated eIF4E-dependent translational control
Open accessAbstract
Hyperconnectivity of neuronal circuits due to increased synaptic protein synthesis is thought to cause autism spectrum disorders (ASDs). The mammalian target of rapamycin (mTOR) is strongly implicated in ASDs by means of upstream signalling; however, downstream regulatory mechanisms are ill-defined. Here we show that knockout of the eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2)-an eIF4E repressor downstream of mTOR-or eIF4E overexpression leads to increased translation of neuroligins, which are postsynaptic proteins that are causally linked to ASDs. Mice that have the gene encoding 4E-BP2 (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviours (that is, social interaction deficits, altered communication and repetitive/stereotyped behaviours). Pharmacological inhibition of eIF4E activity or normalization of neuroligin 1, but not neuroligin 2, protein levels restores the normal excitation/inhibition ratio and rectifies the social behaviour deficits. Thus, translational control by eIF4E regulates the synthesis of neuroligins, maintaining the excitation-to-inhibition balance, and its dysregulation engenders ASD-like phenotypes.
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“Consistently, we found that MIA alters key components of the TSC/mTOR signaling pathway with ultimate activation of the translation initiation factor EIF4E which is predicted to alter the regulation of neural progenitor cell divisions during midgestation [127, 156–158].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [158]
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“This hypothesis has been further elaborated by Santini and Klann and others, with new evidence supporting the crucial role of cap-dependent translation protein EIF4E79, 88, 100, 101 in ASD pathophysiology.77”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [100]
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Citations
Cites
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
Self-citationModel of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768
Neocortical excitation/inhibition balance in information processing and social dysfunction
Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’Shea, D. J., Sohal, V. S., Goshen, I., Finkelstein, J., Paz, J. T., et al. (2011) · Nature · doi:10.1038/nature10360 · Cited by 2,454
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165
Epidemiology of Pervasive Developmental Disorders
Fombonne, E. (2009) · Pediatric Research · doi:10.1203/pdr.0b013e31819e7203 · Cited by 1,971
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
Peça, J., Feliciano, C., Ting, J. T., Wang, W., Wells, M. F., Venkatraman, T. N., Lascola, C. D., Fu, Z., & Feng, G. (2011) · Nature · doi:10.1038/nature09965 · Cited by 1,570
Behavioural phenotyping assays for mouse models of autism
Silverman, J. L., Yang, M., Lord, C., & Crawley, J. N. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2851 · Cited by 1,462
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
Glessner, J. T., Wang, K., Cai, G., Korvatska, O., Kim, C. E., Wood, S., Zhang, H., Estes, A., Brune, C. W., Bradfield, J. P., et al. (2009) · Nature · doi:10.1038/nature07953 · Cited by 1,421
Pause, A., Belsham, G. J., Gingras, A., Donzé, O., Lin, T.-A., Lawrence, J. C., & Sonenberg, N. (1994) · Nature · doi:10.1038/371762a0 · Cited by 1,242
Self-citationDysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes
Chao, H.-T., Chen, H., Samaco, R. C., Xue, M., Chahrour, M., Yoo, J., Neul, J. L., Gong, S., Lu, H.-C., Heintz, N., et al. (2010) · Nature · doi:10.1038/nature09582 · Cited by 1,168
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Kalinowska, M., van der Lei, M. B., Kitiashvili, M., Mamcarz, M., Oliveira, M. M., Longo, F., & Klann, E. (2022) · Figshare · doi:10.6084/m9.figshare.20193624
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Lister, K. C., Wong, C., Uttam, S., Parisien, M., Stecum, P., Brown, N., Cai, W., Ho-Tieng, D., Hooshmandi, M., Gu, N., et al. (2026) · eLife · doi:10.7554/elife.100451.2.sa0
Self-citationLister, K. C., Wong, C., Uttam, S., Parisien, M., Stecum, P., Brown, N., Cai, W., Ho-Tieng, D., Hooshmandi, M., Gu, N., et al. (2026) · eLife · doi:10.7554/elife.100451.2
Self-citationAltered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder
Aaltonen, A., Razquin, J., Garton, D. R., Oyrer, J., Criscuolo, C., Lieberman, O. J., Klann, E., Borgkvist, A., & Santini, E. (2026) · iScience · doi:10.1016/j.isci.2026.117278
The emerging role of gene therapy in autism spectrum disorder
Shokoohi, M., Ghamin, K., Ghaderi, M., Bamarinejad, F., Baker, A. H., Danafar, N., & Zafarshamspour, S. (2026) · Discover Mental Health · doi:10.1007/s44192-026-00425-4
Regulation of the protein synthesis machinery in the striatum
Biever, A. (2016) · theses.fr (ABES) · doi:10.70675/d51e3b2cz4ba2z4930z8686z2d89c7f3949d
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Zhang, P. (2017) · theses.fr (ABES) · doi:10.70675/74cb83e0z6db8z4bb5z838dz6e1bb1c6275f
Locally synthesized glycyl aminoacyl-tRNA synthetase is important for local translation in neurons
de Leon, T. B., Golani‐Armon, A., Cohen, B., & Arava, Y. (2026) · Life Science Alliance · doi:10.26508/lsa.202603630
Lituma, P. J., Deveci, A., Barrio-Alonso, E., Tan, K., Wilkinson, M., Castillo, P. E., & Colak, D. (2026) · eLife · doi:10.7554/elife.111940
Lituma, P. J., Deveci, A., Barrio-Alonso, E., Tan, K., Wilkinson, M. F., Castillo, P. E., & Colak, D. (2026) · eLife · doi:10.7554/elife.111940.1.sa0
Lituma, P. J., Deveci, A., Barrio-Alonso, E., Tan, K., Wilkinson, M., Castillo, P. E., & Colak, D. (2026) · eLife · doi:10.7554/elife.111940.1
Pissarra, M. F., Alpsoy, L., Breyer, M. L., Giossas, V., Jatwani, K., Gkika, K. S., Squire, A., Kuppusamy, M., Oeckinghaus, A., Termathe, M., et al. (2026) · Analytica Chimica Acta · doi:10.1016/j.aca.2026.346265
Self-citationLi, H., Lian, X., Li, Y., Deng, J., Xie, Y., Xie, J., Nie, D., Li, X., Huang, X., & 欧阳岁东 (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06231-x
Jabłońska, J., Orzoł, D., Ciurko, D., Wiera, G., & Mozrzymas, J. W. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111214
BindingDB Entry 50016838: Update on the Development of MNK Inhibitors as Therapeutic Agents.
BindingDB (2023) · UC San Diego · doi:10.7270/q20c50t2
Metadata
- Authors
- Gkogkas, C. G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D. B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., Major, F., Lasko, P., Ruggero, D., Nader, K., Lacaille, J.-C., & Sonenberg, N.
- Affiliations
- McGill University (CA)
- Université de Montréal (CA)
- University of California, San Francisco (US)
- Institute for Research in Immunology and Cancer (CA)
- Corresponding author
- Lacaille, Jean-Claude
- Sonenberg, Nahum
- ORCID
- Venue
- Nature
- Published
- 2012-11-21
- Volume
- 493
- Issue
- 7432
- Pages
- 371-377
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4133997
- OpenAlex
- W2048862315
- Cited by
- 522
- References
- 46
- Citations by year
- 2026: 20 · 2025: 31 · 2024: 23 · 2023: 29 · 2022: 31 · 2021: 27 · 2020: 42 · 2019: 45 · 2018: 33 · 2017: 37 · 2016: 49 · 2015: 59 · 2014: 53 · 2013: 40 · 2012: 2
- FWCI
- 29.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (MOP-114994), MOP93679, MOP-10848, MOP-44050)
- National Cancer Institute (R01CA140456, R01CA154916)
- National Institute of General Medical Sciences (R01GM088813)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- autism spectrum disorder, eIF4E, 4E-BP2, translational regulation, mTOR signaling, neuroligin-1, neuroligin-2, synaptic protein synthesis, excitation-inhibition balance, social interaction deficits, cap-dependent translation, 4EGI-1
- MeSH terms
- Animals, Autistic Disorder, Male, Phenotype, Synapses, Protein Biosynthesis, Cell Adhesion Molecules, Neuronal, Mice, Knockout, Eukaryotic Initiation Factor-4E, Eukaryotic Initiation Factors, Mice
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