ArticleBiological psychiatry2018
Nuclear Excluded Autism-Associated Phosphatase and Tensin Homolog Mutations Dysregulate Neuronal Growth.
Article in Biological psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- PTEN Subcellular Localization Dictates Function.bioRxiv : the preprint server for biology · 2026Article
- Disruption of DNA Repair as an Emerging Epigenetic Mechanism Underlying Autism Spectrum Disorder.Current psychiatry reports · 2026Review
- Impaired nuclear PTEN function drives macrocephaly, lymphadenopathy and late-onset cancer in PTEN hamartoma tumour syndrome.Disease models & mechanisms · 2026Article
- Cancer and Autism: How PTEN Mutations Degrade Function at the Membrane and Isoform Expression in the Human Brain.Journal of molecular biology · 2023Article
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- PTEN Regulates Dendritic Arborization by Decreasing Microtubule Polymerization Rate.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets.Trends in neurosciences · 2021Review
- Integrating thousands of PTEN variant activity and abundance measurements reveals variant subgroups and new dominant negatives in cancers.Genome medicine · 2021Article
- Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity.Molecular autism · 2021Article
- Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes.NPJ genomic medicine · 2021Article
- SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function.EMBO molecular medicine · 2021Article
- Striking a balance: PIPExploration of neuroprotective therapy · 2021Article
- An Integrated Deep-Mutational-Scanning Approach Provides Clinical Insights on PTEN Genotype-Phenotype Relationships.American journal of human genetics · 2020Article
- PTEN Nuclear Functions.Cold Spring Harbor perspectives in medicine · 2020Review
- Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction.Nature communications · 2020Article
- The Role of PTEN in Neurodevelopment.Molecular neuropsychiatry · 2020Review
- PTEN in Autism and Neurodevelopmental Disorders.Cold Spring Harbor perspectives in medicine · 2019Review
- Impact of mTOR hyperactive neurons on the morphology and physiology of adjacent neurons: Do PTEN KO cells make bad neighbors?Experimental neurology · 2019Article
- Pten loss results in inappropriate excitatory connectivity.Molecular psychiatry · 2019Article
- A Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships.American journal of human genetics · 2018Article
Corrections and comments
- Erratum issuedErratum.2021
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPhosphatase and tensin homolog (PTEN) negatively regulates downstream protein kinase B signaling, resulting in decreased cellular growth and proliferation. PTEN is mutated in a subset of children with autism spectrum disorder (ASD); however, the mechanism by which specific point mutations alter PTEN function is largely unknown. Here, we assessed how ASD-associated single-nucleotide variations in PTEN (ASD-PTEN) affect function.
methodsWe used viral-mediated molecular substitution of human PTEN into Pten knockout mouse neurons and assessed neuronal morphology to determine the functional impact of ASD-PTEN. We employed molecular cloning to examine how PTEN's stability, subcellular localization, and catalytic activity affect neuronal growth.
resultsWe identified a set of ASD-PTEN mutations displaying altered lipid phosphatase function and subcellular localization. We demonstrated that wild-type PTEN can rescue the neuronal hypertrophy, while PTEN H93R, F241S, D252G, W274L, N276S, and D326N failed to rescue this hypertrophy. A subset of these mutations lacked nuclear localization, prompting us to examine the role of nuclear PTEN in regulating neuronal growth. We found that nuclear PTEN alone is sufficient to regulate soma size. Furthermore, forced localization of the D252G and W274L mutations into the nucleus partially restores regulation of soma size.
conclusionsASD-PTEN mutations display decreased stability, catalytic activity, and/or altered subcellular localization. Mutations lacking nuclear localization uncover a novel mechanism whereby lipid phosphatase activity in the nucleus can regulate mammalian target of rapamycin signaling and neuronal growth.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.