SHANK proteins: roles at the synapse and in autism spectrum disorder
Open accessAbstract
Several large-scale genomic studies have supported an association between cases of autism spectrum disorder and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3, which encode a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS. An evaluation of human genetic data, as well as of in vitro and in vivo animal model data, may allow us to understand how disruption of SHANK scaffolding proteins affects the structure and function of neural circuits and alters behaviour.
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Rac1 is a converging factor downstream of numerous proteins encoded by high-risk ASD genes.
“Rac1 has been identified as a converging factor downstream of numerous proteins encoded by high-risk ASD genes, such as SHANK 4–6, FMR1 (fragile X mental retardation-1) 7, 8, NRXN 9, and AUTS2 10.”
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 [6]
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- Authors
- Monteiro, P., & Feng, G.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Feng, Guoping
- ORCID
- Feng, Guoping
- Venue
- Nature Reviews Neuroscience
- Published
- 2017-02-09
- Volume
- 18
- Issue
- 3
- Pages
- 147-157
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2586432482
- Cited by
- 681
- References
- 30
- Citations by year
- 2026: 69 · 2025: 77 · 2024: 89 · 2023: 78 · 2022: 77 · 2021: 84 · 2020: 63 · 2019: 58 · 2018: 58 · 2017: 28
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (publishedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health (R01MH097104)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Shank1, Shank2, SHANK3, autism spectrum disorder, postsynaptic scaffolding proteins, glutamatergic synapses, neural circuits, genetic mutations, animal models of autism
- MeSH terms
- Autism Spectrum Disorder, Animals, Child Development Disorders, Pervasive, Humans, Mutation, Nerve Tissue Proteins, Neurons, Synapses
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