JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse
Open accessAbstract
Autism spectrum disorder (ASD) is a heritable, common neurodevelopmental disorder with diverse genetic causes. Several studies have implicated protein synthesis as one among several of its potential convergent mechanisms. We originally identified Janus kinase and microtubule-interacting protein 1 (JAKMIP1) as differentially expressed in patients with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome. Here, we provide multiple lines of evidence that JAKMIP1 is a component of polyribosomes and an RNP translational regulatory complex that includes fragile X mental retardation protein, DEAD box helicase 5, and the poly(A) binding protein cytoplasmic 1. JAKMIP1 loss dysregulates neuronal translation during synaptic development, affecting glutamatergic NMDAR signaling, and results in social deficits, stereotyped activity, abnormal postnatal vocalizations, and other autistic-like behaviors in the mouse. These findings define an important and novel role for JAKMIP1 in neural development and further highlight pathways regulating mRNA translation during synaptogenesis in the genesis of neurodevelopmental disorders.
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p70S6K is a kinase essential for switching on translation initiation.
“First, Rac1 appears to activate mTOR and its downstream target p70S6K (70-kDa ribosomal S6 kinase) 57, 58, a kinase essential for switching on translation initiation 48, 49.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [49]
The Discussion (page unavailable) says that PABPC1 is required for translation initiation, but it does not make that statement about p70S6K. Searches for p70S6K, S6K, and the claimed kinase role found no passage in our copy addressing whether p70S6K is essential for switching on translation initiation. (LLM, conf=0.76)
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- Authors
- Berg, J. M., Lee, C., Chen, L., Galvan, L., Cepeda, C., Chen, J. Y., Peñagarikano, O., Stein, J. L., Li, A., Oguro-Ando, A., Miller, J. A., Vashisht, A. A., Starks, M. E., Kite, E. P., Tam, E., Gdalyahu, A., Al-Sharif, N. B., Burkett, Z. D., White, S. A., Fears, S. C., Levine, M. S., Wohlschlegel, J. A., & Geschwind, D. H.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Geschwind, Daniel H.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 88
- Issue
- 6
- Pages
- 1173-1191
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4829343
- OpenAlex
- W2173629501
- Cited by
- 45
- References
- 14
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 9 · 2017: 4 · 2016: 3 · 2015: 1
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- HAL (submittedVersion)
- Funders
- Autism Speaks
- Regeneron Pharmaceuticals
- National Institutes of Health (U42OD011175)
- U.S. Public Health Service (NIH/NIMHR01MH081754, NIH/NICHD P50HD055784, NIH/NIMHF31MH088083, NIH/NIMH K99MH102357, NIH/NIGMS R01GM089778, NIH/NIMH R01MH070712, NIH/NIMH K08MH086786, NIH/NIMH T32MH073526, NIH/NICHD P30HD004612)
- University of California, Davis (U42RR024244)
- National Institute of Mental Health (K99MH102357, K08MH086786, R01MH100027, R01MH070712, R01MH081754, F31MH088083, T32MH073526)
- National Human Genome Research Institute (U01HG004085, U54HG006364, U01HG004080)
- National Institute of General Medical Sciences (T32GM065823, R01GM089778)
- National Center for Research Resources (U42RR024244)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD055784, P30HD004612)
- 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, synaptic development, polysomes, RNA-binding protein complex, FMRP, PABP1, NMDA receptor signaling, glutamatergic synapses, social dysfunction, stereotypy, neurodevelopmental disorders, fragile X syndrome
- MeSH terms
- Autism Spectrum Disorder, Animals, Male, Mice, Inbred C57BL, Neurons, Synapses, Protein Biosynthesis, RNA-Binding Proteins, Mice, Knockout, Proteomics, Adaptor Proteins, Signal Transducing, Mice, Gene Regulatory Networks
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