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Psychosis Risk Candidate ZNF804A Localizes to Synapses and Regulates Neurite Formation and Dendritic Spine Structure.
Deans, P J Michael; Raval, Pooja; Sellers, Katherine J; Gatford, Nicholas J F; Halai, Sanjay; Duarte, Rodrigo R R; Shum, Carole; Warre-Cornish, Katherine; Kaplun, Victoria E; Cocks, Graham; Hill, Matthew; Bray, Nicholas J; Price, Jack; Srivastava, Deepak P.
Afiliación
  • Deans PJM; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Raval P; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Sellers KJ; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Gatford NJF; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Halai S; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Duarte RRR; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Shum C; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Warre-Cornish K; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Kaplun VE; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Cocks G; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London.
  • Hill M; MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff, United Kingdom; Neuroscience and Mental Health Research Institute, College of Biomedical and Life Sciences, Cardiff University School of Medicine, Cardiff University, Cardiff, United Kingdom.
  • Bray NJ; MRC Centre for Neuropsychiatric Genetics & Genomics, Cardiff, United Kingdom.
  • Price J; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London; MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London; United Kingdom.
  • Srivastava DP; Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London; MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London; United Kingdom.
Biol Psychiatry ; 82(1): 49-61, 2017 07 01.
Article en En | MEDLINE | ID: mdl-27837918
BACKGROUND: Variation in the gene encoding zinc finger binding protein 804A (ZNF804A) is associated with schizophrenia and bipolar disorder. Evidence suggests that ZNF804A is a regulator of gene transcription and is present in nuclear and extranuclear compartments. However, a detailed examination of ZNF804A distribution and its neuronal functions has yet to be performed. METHODS: The localization of ZNF804A protein was examined in neurons derived from human neural progenitor cells, human induced pluripotent stem cells, or in primary rat cortical neurons. In addition, small interfering RNA-mediated knockdown of ZNF804A was conducted to determine its role in neurite formation, maintenance of dendritic spine morphology, and responses to activity-dependent stimulations. RESULTS: Endogenous ZNF804A protein localized to somatodendritic compartments and colocalized with the putative synaptic markers in young neurons derived from human neural progenitor cells and human induced pluripotent stem cells. In mature rat neurons, Zfp804A, the homolog of ZNF804A, was present in a subset of dendritic spines and colocalized with synaptic proteins in specific nanodomains, as determined by super-resolution microscopy. Interestingly, knockdown of ZNF804A attenuated neurite outgrowth in young neurons, an effect potentially mediated by reduced neuroligin-4 expression. Furthermore, knockdown of ZNF804A in mature neurons resulted in the loss of dendritic spine density and impaired responses to activity-dependent stimulation. CONCLUSIONS: These data reveal a novel subcellular distribution for ZNF804A within somatodendritic compartments and a nanoscopic organization at excitatory synapses. Moreover, our results suggest that ZNF804A plays an active role in neurite formation, maintenance of dendritic spines, and activity-dependent structural plasticity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Neuritas / Espinas Dendríticas / Factores de Transcripción de Tipo Kruppel Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Biol Psychiatry Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sinapsis / Neuritas / Espinas Dendríticas / Factores de Transcripción de Tipo Kruppel Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Biol Psychiatry Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos