Schizophrenia risk ZNF804A interacts with its associated proteins to modulate dendritic morphology and synaptic development
| Autor: | Joseph Mao, Fengping Dong, Joy Yoon, Yingwei Mao, Miranda Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Neurite Dendritic Spines Kruppel-Like Transcription Factors Dendritic morphology Gene dosage lcsh:RC346-429 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Risk Factors Neurites Animals Humans Genetic Predisposition to Disease Molecular Biology lcsh:Neurology. Diseases of the nervous system Zinc finger Gene knockdown biology Research Ribosomal protein SA Brain Dendrites Cell biology Mice Inbred C57BL 030104 developmental biology Gene Knockdown Techniques Synapses biology.protein Schizophrenia Female Neural development FEZ1 ZNF804A binding proteins 030217 neurology & neurosurgery Zinc finger protein 804A ZNF804A Protein Binding |
| Zdroj: | Molecular Brain Molecular Brain, Vol 14, Iss 1, Pp 1-12 (2021) |
| ISSN: | 1756-6606 |
| Popis: | Schizophrenia (SZ) is a devastating brain disease that affects about 1% of world population. Among the top genetic associations,zinc finger protein 804A(ZNF804A) gene encodes a zinc finger protein, associated with SZ and biolar disorder (BD). Copy number variants (CNVs) ofZNF804Ahave been observed in patients with autism spectrum disorders (ASDs), anxiety disorder, and BD, suggesting thatZNF804Ais a dosage sensitive gene for brain development. However, its molecular functions have not been fully determined. Our previous interactomic study revealed that ZNF804A interacts with multiple proteins to control protein translation and neural development. ZNF804A is localized in the cytoplasm and neurites in the human cortex and is expressed in various types of neurons, including pyramidal, dopaminergic, GABAergic, and Purkinje neurons in mouse brain. To further examine the effect of gene dosage ofZNF804Aon neurite morphology, both knockdown and overexpression ofZNF804Ain primary neuronal cells significantly attenuate dendritic complex and spine formation. To determine the factors mediating these phenotypes, interestingly, three binding proteins of ZNF804A, galectin 1 (LGALS1), fasciculation and elongation protein zeta 1 (FEZ1) and ribosomal protein SA (RPSA), show different effects on reversing the deficits. LGALS1 and FEZ1 stimulate neurite outgrowth at basal level but RPSA shows no effect. Intriguingly, LGALS1 but not FEZ1, reverses the neurite outgrowth deficits induced by ZNF804A knockdown. However, FEZ1 and RPSA but not LGALS1, can ameliorate ZNF804A overexpression-mediated dendritic abnormalities. Thus, our results uncover a critical post-mitotic role of ZNF804A in neurite and synaptic development relevant to neurodevelopmental pathologies. |
| Databáze: | OpenAIRE |
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