GO:0150035 regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission: Synaptic Plasticity Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0150035 describes the biological process that modulates the frequency, rate, or extent of trans-synaptic signaling mediated by brain-derived neurotrophic factor (BDNF).
• BDNF release and subsequent signaling are key regulators of synaptic transmission and long-term potentiation, processes dependent on proteins such as synaptotagmin-IV.
• Copine-6 regulates dendritic spine morphology in hippocampal neurons, a structural correlate of BDNF-modulated synaptic transmission.
• Dysregulation of this process is implicated in neurodevelopmental and neurodegenerative disorders, making it a target for gene editing research.
• CRISPR-based knockout, point mutation, knock-in, and overexpression models enable causal dissection of genes within GO:0150035.
• Understanding this term helps researchers design experiments linking BDNF signaling to synaptic function and disease.
Description
GO:0150035, regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission, is a biological process that encompasses any mechanism controlling the frequency, rate, or extent of BDNF-dependent signaling across synapses. BDNF is a neurotrophin that influences synaptic plasticity, and its release and downstream actions are tightly regulated to modulate neurotransmission. This term is critical for researchers studying how neural circuits adapt, because alterations in BDNF signaling are linked to cognitive and neurological conditions. Experimental evidence shows that proteins such as synaptotagmin-IV modulate synaptic function and long-term potentiation by regulating BDNF release. Additionally, Copine-6 regulates dendritic spine morphology in hippocampal neurons, providing a structural basis for BDNF-modulated synaptic transmission. Thus, GO:0150035 provides a framework to investigate molecular players that control BDNF-dependent synaptic signaling.
regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission At A Glance
| GO ID | GO:0150035 |
|---|---|
| GO term | regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission |
| Ontology | biological_process |
| Synonym | None |
| Major function | Modulates the frequency, rate, or extent of BDNF-mediated trans-synaptic signaling to control synaptic transmission |
| Related molecules | BDNF, synaptotagmin-IV, Copine-6 |
| Associated processes | Synaptic plasticity, long-term potentiation, dendritic spine morphology |
| Research relevance | Implicated in neurodevelopmental and neurodegenerative disorders; target for CRISPR-based functional studies |
What Is GO:0150035?
According to the Gene Ontology, GO:0150035 is defined as any process that modulates the frequency, rate or extent of trans-synaptic signaling by BDNF, modulating synaptic transmission. In other words, it covers the regulatory events that adjust how BDNF signals across a synapse to influence the strength or efficacy of synaptic transmission.
Why Is regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission Important in Cell Biology?
GO:0150035 is important because BDNF-dependent regulation of synaptic transmission is a core mechanism of synaptic plasticity, learning, and memory. Disruptions in this process contribute to neurological and psychiatric disorders, and understanding the regulatory components can reveal therapeutic targets. Experimental studies have shown that synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release, while Copine-6 controls dendritic spine morphology in hippocampal neurons. These findings highlight the importance of this GO term for both basic neuroscience and translational research.
• BDNF signaling is essential for synaptic plasticity and long-term potentiation.
• Synaptotagmin-IV regulates BDNF release, directly impacting synaptic function.
• Copine-6 influences dendritic spine morphology, a structural correlate of synaptic transmission.
• Dysregulation of BDNF signaling is linked to neurodegenerative and neurodevelopmental disorders.
• The process is a target for understanding learning and memory mechanisms.
• CRISPR screens can identify novel regulators within this GO term.
• Animal models with mutations in BDNF pathway genes help dissect disease mechanisms.
• The term bridges molecular neuroscience and clinical research.
• It provides a framework for studying trans-synaptic signaling in health and disease.
• Experimental tools such as knockout and knock-in models enable causal testing of candidate genes.
What Happens During regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission?
BDNF Release and Synaptotagmin-IV Regulation
In simple terms: BDNF is packaged and released from neurons, and synaptotagmin-IV helps control how much is released.
BDNF is released from presynaptic terminals in an activity-dependent manner. Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release, as shown in studies of hippocampal neurons. This regulation ensures that BDNF availability is matched to synaptic activity, thereby influencing trans-synaptic signaling.
BDNF Signaling at the Synapse
In simple terms: Once released, BDNF binds to receptors on the postsynaptic neuron to trigger signaling.
BDNF acts on its receptors, such as TrkB, to initiate intracellular signaling cascades that modulate synaptic transmission. This process is part of the broader regulation of trans-synaptic signaling by BDNF, and its modulation affects synaptic strength and plasticity.
Dendritic Spine Morphology and Copine-6
In simple terms: Copine-6 helps shape the tiny protrusions on neurons where synapses form.
Copine-6 regulates dendritic spine morphology in hippocampal neurons, which is a structural component of BDNF-modulated synaptic transmission. Changes in spine morphology can alter synaptic efficacy, linking structural plasticity to functional regulation within GO:0150035.
Modulation of Synaptic Transmission
In simple terms: The combined actions of BDNF and its regulators change how strongly neurons communicate.
The regulation of trans-synaptic signaling by BDNF ultimately modulates synaptic transmission by altering the frequency, rate, or extent of signaling. This is evidenced by studies showing that synaptotagmin-IV affects long-term potentiation through BDNF release, and that Copine-6 influences spine morphology.
Key Genes Involved in GO:0150035 regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission
The following genes and proteins are experimentally linked to the regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission.
| Gene | Major Role | Research Relevance |
|---|---|---|
| BDNF | Neurotrophin that signals across synapses to modulate transmission | Central to GO:0150035; target for knockout and overexpression studies |
| SYT4 | Regulates BDNF release and synaptic function | Modulates long-term potentiation |
| CPNE6 | Regulates dendritic spine morphology in hippocampal neurons | Structural regulator of synaptic transmission |
| NTRK2 | BDNF receptor (TrkB) mediating downstream signaling | Key mediator of BDNF effects on synaptic transmission |
| SYP | Synaptic vesicle protein involved in neurotransmitter release | Potential downstream target of BDNF signaling |
| DLG4 | Postsynaptic scaffolding protein (PSD-95) | Organizes postsynaptic signaling complexes |
| GRIN1 | NMDA receptor subunit | Mediates synaptic plasticity influenced by BDNF |
| GRIN2A | NMDA receptor subunit | Modulates synaptic transmission and plasticity |
| GRIN2B | NMDA receptor subunit | Involved in BDNF-dependent synaptic changes |
| CAMK2A | Calcium/calmodulin-dependent protein kinase II | Downstream effector of BDNF signaling |
| CREB1 | Transcription factor activated by BDNF signaling | Regulates gene expression for synaptic plasticity |
| ARC | Activity-regulated cytoskeleton-associated protein | Required for synaptic plasticity and BDNF effects |
| HOMER1 | Postsynaptic density scaffolding protein | Links BDNF signaling to metabotropic glutamate receptors |
| SHANK3 | Postsynaptic scaffolding protein | Associated with synaptic transmission and neurodevelopmental disorders |
| BDNF-AS | Long non-coding RNA antisense to BDNF | Regulates BDNF expression |
| MAPK1 | Mitogen-activated protein kinase 1 | Downstream of BDNF-TrkB signaling |
| AKT1 | Protein kinase B | Survival and plasticity signaling downstream of BDNF |
| PIK3CA | Phosphatidylinositol 3-kinase catalytic subunit | Part of BDNF signaling pathways |
How Is regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission Regulated?
The process of regulation of trans-synaptic signaling by BDNF is itself regulated at multiple levels. Synaptotagmin-IV controls BDNF release, thereby modulating synaptic function and long-term potentiation. Additionally, Copine-6 regulates dendritic spine morphology, which can influence the efficacy of BDNF signaling. These regulatory mechanisms ensure that BDNF-dependent synaptic transmission is appropriately tuned to neuronal activity.
regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BDNF | Alzheimer's disease, depression | Knockout and overexpression models in neurons |
| SYT4 | Epilepsy, synaptic plasticity disorders | Point mutation knock-in to alter BDNF release |
| CPNE6 | Neurodevelopmental disorders | Knockout and tagged knock-in for spine morphology |
| SHANK3 | Autism spectrum disorder | Knockout and point mutation models |
| NTRK2 | Mood disorders, obesity | Conditional knockout and knock-in |
Neurodevelopmental Disorders
Alterations in BDNF signaling and synaptic transmission are associated with neurodevelopmental disorders such as autism spectrum disorders and schizophrenia. Genes like SHANK3 and CPNE6, which regulate synaptic structure and function, have been implicated in these conditions.
Neurodegenerative Diseases
Reduced BDNF signaling is observed in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. The regulation of trans-synaptic signaling by BDNF is critical for neuronal survival and plasticity, and its dysregulation may contribute to disease progression.
Epilepsy and Seizure Susceptibility
Abnormal BDNF signaling can lead to hyperexcitability and seizures. Synaptotagmin-IV, which regulates BDNF release, has been studied in the context of synaptic function and long-term potentiation, processes that are disrupted in epilepsy.
From regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SYT4 affect BDNF release and synaptic transmission? | SYT4 knockout neurons |
| How does CPNE6 mutation alter dendritic spine morphology? | CPNE6 point mutation knock-in |
| Can overexpression of BDNF rescue synaptic deficits? | BDNF overexpression lentiviral model |
| What is the role of NTRK2 in BDNF-modulated transmission? | NTRK2 conditional knockout |
| Does a disease-associated SHANK3 variant impair synaptic signaling? | SHANK3 knock-in of patient mutation |
| Which genes regulate BDNF-dependent synaptic transmission? | CRISPR library screening in primary neurons |
How to Study the regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Patch-clamp electrophysiology | Synaptic currents and plasticity | Assessing BDNF modulation of transmission |
| Field potential recording | Long-term potentiation | Studying synaptic plasticity |
| Confocal microscopy | Dendritic spine density and morphology | Evaluating Copine-6 effects |
| Western blot | Protein expression levels | Quantifying BDNF and signaling proteins |
| ELISA | BDNF concentration | Measuring release in culture media |
| RNA-seq | Transcriptional changes | Identifying genes regulated by BDNF signaling |
| CRISPR screening | Gene function at scale | Discovering novel regulators of GO:0150035 |
| Bioinformatics pathway analysis | Enrichment of GO terms | Linking candidate genes to synaptic transmission |
Electrophysiology
Patch-clamp recordings and field potential recordings measure synaptic transmission and long-term potentiation, directly assessing the functional output of GO:0150035. Studies of synaptotagmin-IV have used such methods to link BDNF release to synaptic function.
Imaging of Dendritic Spines
Confocal or two-photon microscopy visualizes dendritic spine morphology, as demonstrated for Copine-6 in hippocampal neurons. This provides structural evidence for regulation of synaptic transmission.
Molecular Biology and Biochemistry
Western blotting, co-immunoprecipitation, and ELISA can quantify BDNF protein levels and interactions. These methods help identify regulators within the GO:0150035 process.
CRISPR Screening and Bioinformatics
Pooled CRISPR screens combined with next-generation sequencing can identify genes that modulate BDNF signaling. Bioinformatics analysis of transcriptomic data can reveal pathways associated with GO:0150035.
How CRISPR Can Be Used to Study GO:0150035 regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission
Knockout
CRISPR knockout of genes such as SYT4 or CPNE6 can abolish their function, allowing researchers to test their necessity in BDNF-modulated synaptic transmission. For example, SYT4 knockout reduces BDNF release and impairs long-term potentiation.
Point Mutation
Introducing precise point mutations via CRISPR base editing or homology-directed repair can mimic disease-associated variants. This helps dissect how specific amino acid changes in proteins like CPNE6 affect dendritic spine morphology and synaptic function.
Knock-in
Knock-in of reporter tags or disease alleles enables visualization and functional analysis of endogenous proteins. Tagged knock-in of BDNF or its regulators can reveal real-time dynamics of trans-synaptic signaling.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression can increase BDNF levels or its regulators, testing sufficiency in enhancing synaptic transmission. This approach is useful for rescue experiments in disease models.
How EDITGENE Supports regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission Research
Researchers studying regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission-related genes often need to determine whether a candidate gene is causally involved in synaptic function or disease. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell and animal models, enabling functional validation of genes within GO:0150035.
Contact EDITGENE today to design your custom CRISPR model for regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission research.
Frequently Asked Questions About regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission
What is GO:0150035?
GO:0150035 is a Gene Ontology biological process term defined as any process that modulates the frequency, rate or extent of trans-synaptic signaling by BDNF, modulating synaptic transmission.
What genes are involved in regulation of trans-synaptic signaling by BDNF?
Key genes include BDNF, SYT4, CPNE6, NTRK2, and SHANK3, among others.
How does BDNF modulate synaptic transmission?
BDNF is released from neurons and binds to receptors, triggering signaling cascades that alter synaptic strength; this release is regulated by proteins such as synaptotagmin-IV.
What is the role of synaptotagmin-IV in BDNF signaling?
Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release.
How does Copine-6 relate to synaptic transmission?
Copine-6 regulates dendritic spine morphology in hippocampal neurons, a structural component of BDNF-modulated synaptic transmission.
Which diseases are associated with dysregulation of this process?
Neurodevelopmental disorders, neurodegenerative diseases, and epilepsy have been linked to altered BDNF signaling and synaptic transmission.
What experimental models are used to study GO:0150035?
Common models include knockout mice, point mutation knock-in, overexpression, and CRISPR screens in neuronal cells.
How can CRISPR help study BDNF-modulated synaptic transmission?
CRISPR enables precise knockout, point mutation, knock-in, and overexpression of genes like SYT4 and CPNE6 to test their causal roles.
What methods measure synaptic transmission regulated by BDNF?
Electrophysiology, imaging of dendritic spines, and molecular assays such as ELISA and Western blot are commonly used.
Why is GO:0150035 important for neuroscience?
It provides a framework for understanding how BDNF signaling is regulated to control synaptic plasticity, learning, and memory, with implications for neurological disorders.
Conclusion
GO:0150035, regulation of trans-synaptic signaling by BDNF, modulating synaptic transmission, is a fundamental biological process that integrates BDNF release, receptor signaling, and structural plasticity. Experimental evidence highlights key regulators such as synaptotagmin-IV and Copine-6. Understanding this process is essential for deciphering synaptic function in health and disease. CRISPR-based models from EDITGENE can accelerate discovery of novel regulators and therapeutic targets within this pathway.
References
- 1. Burk K et al.. 2018. Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6.. Cereb Cortex 28(4):1087-1104 PMID: 28158493
- 2. Dean C et al.. 2009. Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release.. Nat Neurosci 12(6):767-76 PMID: 19448629
