ArticleMolecular psychiatry2023
The cytoplasmic localization of ADNP through 14-3-3 promotes sex-dependent neuronal morphogenesis, cortical connectivity, and calcium signaling.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- ADNP Functions During Early Brain Development and Their Relevance to ASD and ADNP Syndrome.International journal of molecular sciences · 2026Review
- An Adnp frameshift variant disrupts Wnt signalling inducing chromatocytoskeletal defects and autism-related behaviour in male mice.EBioMedicine · 2026Article
- Concordant transcriptional and morphological remodeling revealed bybioRxiv : the preprint server for biology · 2026Article
- ADNP missense variant p.C687R disrupts chromatin regulation and GABAergic differentiation in Helsmoortel-Van der Aa syndrome.Molecular autism · 2026Article
- Chromatin remodelling subunit SMARCB1 is implicated in dendrite development and complex brain functions.Acta neuropathologica communications · 2026Article
- Cadherin 11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit.Molecular psychiatry · 2026Article
- A frameshift variant in activity-dependent neuroprotective protein (ADNP) causes nucleocytoskeletal alterations in a dizygotic male twin: a case study.Clinical epigenetics · 2025Article
- CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning.Molecular psychiatry · 2025Article
- Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP.Neurogenetics · 2025Article
- The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles ofbioRxiv : the preprint server for biology · 2024Article
- Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity.Journal of molecular neuroscience : MN · 2024Article
- Genetic and Environmental Factors Co-Contributing to Behavioral Abnormalities inInternational journal of molecular sciences · 2024Article
- ADNP dysregulates methylation and mitochondrial gene expression in the cerebellum of a Helsmoortel-Van der Aa syndrome autopsy case.Acta neuropathologica communications · 2024Article
- Clinical impact and in vitro characterization of ADNP variants in pediatric patients.Molecular autism · 2024Article
- Ex Vivo Live Imaging in Brain Slices for Analysis of Neurite Formation in Combination with In Utero Electroporation.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Unexpected gender differences in progressive supranuclear palsy reveal efficacy for davunetide in women.Translational psychiatry · 2023Article
- Article
- Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism.Clinical epigenetics · 2023Review
- Helsmoortel-van der Aa syndrome in a Chinese pediatric patient due toFrontiers in pediatrics · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Defective neuritogenesis is a contributing pathogenic mechanism underlying a variety of neurodevelopmental disorders. Single gene mutations in activity-dependent neuroprotective protein (ADNP) are the most frequent among autism spectrum disorders (ASDs) leading to the ADNP syndrome. Previous studies showed that during neuritogenesis, Adnp localizes to the cytoplasm/neurites, and Adnp knockdown inhibits neuritogenesis in culture. Here, we hypothesized that Adnp is localized in the cytoplasm during neurite formation and that this process is mediated by 14-3-3. Indeed, applying the 14-3-3 inhibitor, difopein, blocked Adnp cytoplasmic localization. Furthermore, co-immunoprecipitations showed that Adnp bound 14-3-3 proteins and proteomic analysis identified several potential phosphorylation-dependent Adnp/14-3-3 binding sites. We further discovered that knockdown of Adnp using in utero electroporation of mouse layer 2/3 pyramidal neurons in the somatosensory cortex led to previously unreported changes in neurite formation beginning at P0. Defects were sustained throughout development, the most notable included increased basal dendrite number and axon length. Paralleling the observed morphological aberrations, ex vivo calcium imaging revealed that Adnp deficient neurons had greater and more frequent spontaneous calcium influx in female mice. GRAPHIC, a novel synaptic tracing technology substantiated this finding, revealing increased interhemispheric connectivity between female Adnp deficient layer 2/3 pyramidal neurons. We conclude that Adnp is localized to the cytoplasm by 14-3-3 proteins, where it regulates neurite formation, maturation, and functional cortical connectivity significantly building on our current understanding of Adnp function and the etiology of ADNP syndrome.
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