ArticlePLoS genetics2016
A Jacob/Nsmf Gene Knockout Results in Hippocampal Dysplasia and Impaired BDNF Signaling in Dendritogenesis.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- NSMF modulates replication stress to facilitate colorectal cancer progression.Nucleic acids research · 2026Article
- Excitation-transcription coupling, neuronal gene expression and synaptic plasticity.Nature reviews. Neuroscience · 2023Review
- Activation of TrkB signaling mitigates cerebellar anomalies caused by Rbm4-Bdnf deficiency.Communications biology · 2023Article
- Alteration of replication protein A binding mode on single-stranded DNA by NSMF potentiates RPA phosphorylation by ATR kinase.Nucleic acids research · 2023Article
- Integration of nuclear CaCellular and molecular life sciences : CMLS · 2023Article
- Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease.The EMBO journal · 2023Article
- A Jacob/nsmf gene knockout does not protect against acute hypoxia- and NMDA-induced excitotoxic cell death.Molecular brain · 2023Article
- Brain-specific deletion of GIT1 impairs cognition and alters phosphorylation of synaptic protein networks implicated in schizophrenia susceptibility.Molecular psychiatry · 2022Article
- Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance, neuroinflammation and Alzheimer's disease.Translational neurodegeneration · 2022Article
- A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain.Nature communications · 2021Article
- Jacob, a Synapto-Nuclear Protein Messenger Linking N-methyl-D-aspartate Receptor Activation to Nuclear Gene Expression.Frontiers in synaptic neuroscience · 2021Review
- Fetal Bisphenol-A Induced Changes in Murine Behavior and Brain Gene Expression Persisted in Adult-aged Offspring.Endocrinology · 2020Article
- The Synaptonuclear Messenger RNF10 Acts as an Architect of Neuronal Morphology.Molecular neurobiology · 2019Article
- Physical Activity and Brain Health.Genes · 2019Review
- Myosin V regulates synaptopodin clustering and localization in the dendrites of hippocampal neurons.Journal of cell science · 2019Article
- Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments.Frontiers in pharmacology · 2019Article
- In vivo regulation of the A disintegrin and metalloproteinase 10 (ADAM10) by the tetraspanin 15.Cellular and molecular life sciences : CMLS · 2018Article
- Calmodulin shuttling mediates cytonuclear signaling to trigger experience-dependent transcription and memory.Nature communications · 2018Article
- Regulated transport of signaling proteins from synapse to nucleus.Current opinion in neurobiology · 2017Review
- Posttranslational modification impact on the mechanism by which amyloid-β induces synaptic dysfunction.EMBO reports · 2017Article
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Authors and funding
26 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Jacob, the protein encoded by the Nsmf gene, is involved in synapto-nuclear signaling and docks an N-Methyl-D-Aspartate receptor (NMDAR)-derived signalosome to nuclear target sites like the transcription factor cAMP-response-element-binding protein (CREB). Several reports indicate that mutations in NSMF are related to Kallmann syndrome (KS), a neurodevelopmental disorder characterized by idiopathic hypogonadotropic hypogonadism (IHH) associated with anosmia or hyposmia. It has also been reported that a protein knockdown results in migration deficits of Gonadotropin-releasing hormone (GnRH) positive neurons from the olfactory bulb to the hypothalamus during early neuronal development. Here we show that mice that are constitutively deficient for the Nsmf gene do not present phenotypic characteristics related to KS. Instead, these mice exhibit hippocampal dysplasia with a reduced number of synapses and simplification of dendrites, reduced hippocampal long-term potentiation (LTP) at CA1 synapses and deficits in hippocampus-dependent learning. Brain-derived neurotrophic factor (BDNF) activation of CREB-activated gene expression plays a documented role in hippocampal CA1 synapse and dendrite formation. We found that BDNF induces the nuclear translocation of Jacob in an NMDAR-dependent manner in early development, which results in increased phosphorylation of CREB and enhanced CREB-dependent Bdnf gene transcription. Nsmf knockout (ko) mice show reduced hippocampal Bdnf mRNA and protein levels as well as reduced pCREB levels during dendritogenesis. Moreover, BDNF application can rescue the morphological deficits in hippocampal pyramidal neurons devoid of Jacob. Taken together, the data suggest that the absence of Jacob in early development interrupts a positive feedback loop between BDNF signaling, subsequent nuclear import of Jacob, activation of CREB and enhanced Bdnf gene transcription, ultimately leading to hippocampal dysplasia.
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