Neurexins control the strength and precise timing of glycinergic inhibition in the auditory brainstem DOI Open Access

He-Hai Jiang,

Ruoxuan Xu,

Xiupeng Nie

et al.

Published: May 14, 2024

Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether how neurexins are involved shaping functional properties of the glycinergic synapses, which mediate prominent inhibition brainstem spinal cord. To address these issues, we examined role a model synapse between principal neuron medial nucleus trapezoid body (MNTB) lateral superior olive (LSO) auditory brainstem. Combining RNAscope with stereotactic injection AAV-Cre MNTB neurexin1/2/3 conditional triple knockout mice, showed that neurons highly express all isoforms although their expression levels vary remarkably. Selective ablation not only reduced amplitude but also altered kinetics synaptic transmission at LSO neurons. The dysfunctions primarily resulted from an impaired Ca 2+ sensitivity release loosened coupling voltage-gated channels vesicles. Together, our current findings demonstrate essential controlling strength temporal precision synapse, therefore corroborates key major types fast chemical

Language: Английский

Cationic peptides cause memory loss through endophilin-mediated endocytosis DOI
Eric Stokes, José Vásquez,

Ghalia Azouz

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Language: Английский

Citations

1
Alternative splicing controls teneurin-3 compact dimer formation for neuronal recognition DOI Creative Commons
Christos Gogou, J. Wouter Beugelink, Cátia P. Frias

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 29, 2024

Abstract Neuronal network formation is facilitated by recognition between synaptic cell adhesion molecules at the surface. Alternative splicing of provides additional specificity in forming neuronal connections. For teneurin family molecules, alternative EGF-repeats and NHL domain controls protein-protein interactions. Here we present cryo-EM structures compact dimeric ectodomain two teneurin-3 isoforms that harbour splice insert EGF-repeats. This dimer stabilised an EGF8-ABD contact subunits. Cryo-EM reconstructions all four variants, together with SAXS negative stain EM, reveal compacted dimers for each, variant-specific arrangements. results specific trans -cellular interactions, as tested clustering stripe assays. The conformations provide a structural basis homo- heterophilic Altogether, our findings demonstrate how rearrangements subunits, influencing likely circuit wiring.

Language: Английский

Citations

7
Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP DOI Creative Commons
Agata Nowacka, Angela M. Getz, Diogo Bessa‐Neto

et al.

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1906)

Published: June 10, 2024

This review focuses on the activity-dependent diffusion trapping of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as a crucial mechanism for expression early long-term potentiation (LTP), process central to learning and memory. Despite decades research, precise mechanisms by which LTP induction leads an increase in AMPAR responses at synapses have been elusive. We different hypotheses that put forward explain increased responsiveness during LTP. discuss dynamic nature complexes, including their constant turnover modifications affect synaptic accumulation. highlight hypothesis suggesting AMPARs are diffusively trapped through interactions with protein-based binding slots post-synaptic density (PSD), offering potential explanation strength Furthermore, we outline challenges still be addressed before fully understand functional roles molecular nanoscale organization article is part discussion meeting issue 'Long-term potentiation: 50 years on'.

Language: Английский

Citations

5
Transient, nano-scale, liquid-like molecular assemblies coming of age DOI Creative Commons
Akihiro Kusumi, Taka A. Tsunoyama, Kenichi Suzuki

et al.

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 89, P. 102394 - 102394

Published: July 3, 2024

This review examines the dynamic mechanisms underlying cellular signaling, communication, and adhesion via transient, nano-scale, liquid-like molecular assemblies on plasma membrane (PM). Traditional views posit that stable, solid-like complexes perform these functions. However, advanced imaging reveals many signaling scaffolding proteins only briefly reside in micron-scale protein PM, including cell structures synapses, are likely made of archipelagoes nanoliquid islands. Borrowing concept liquid–liquid phase separation to form biocondensates, we propose nano-scale oligomers enabled by multiple weak but specific interactions often involving intrinsically disordered regions. The signals from individual would occur as pulses. Single-molecule emerges a crucial technique for characterizing transient suggesting shift toward model where fluidity underpins signal regulation integration.

Language: Английский

Citations

4
Tuning synapse strength by nanocolumn plasticity DOI
Na Xu, Siyu Chen, Ai‐Hui Tang

et al.

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Neurexin 3 is differentially methylated and downregulated following chronic ethanol use. DOI Creative Commons
Clara C. Lowe,

Frances Miller,

Dongqin Zhu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Abstract Background: Increasing evidence confirms the value of unbiased epigenomic and transcriptomic profiling in identification neuroadaptations alcohol use disorder (AUD). Through this integrated omics analysis, we identified neurexin3 (NRXN3) as a critical player mediating alcohol’s effects on cortex primates mice. Neurexins are presynaptic cell adhesion molecules synaptic adaptations. Although has been linked to substance disorders, specific regulatory mechanisms that enable NRXN3’s transcript/isoform diversity downstream dynamics contributing AUD remain unknown. Methods: We conducted genome-wide DNA methylation (DNAm) RNAseq analyses dorsolateral prefrontal (dlPFC) rhesus macaques remained alcohol-naïve (controls) or self-administered ethanol for 12 months. qPCR immunohistochemistry were used measure levels Nrxn3 transcripts isoforms parvalbumin interneurons prelimbic (PLC) mice following chronic exposure. Results: Our sex-specific differences DNAm gene expression. However, there was shared enrichment signaling pathways neurotransmission plasticity. Specifically, found differential mapping NRXN3, downregulation transcript NRXN3b. further showed conserved use, occurred PLC. Conclusions: research provides significant insights into complex by which affects expression NRXN3within PFC/PLC how might be modulating plasticity type manner.

Language: Английский

Citations

0
Essential Role of Latrophilin-1 Adhesion GPCR Nanoclusters in Inhibitory Synapses DOI

Daniel Mat,

Jaybree M. Lopez, Richard Sando

et al.

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(23), P. e1978232024 - e1978232024

Published: April 29, 2024

Latrophilin-1 (Lphn1, aka CIRL1 and CL1; gene symbol

Language: Английский

Citations

3
Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity DOI Creative Commons

Guilian Tian,

Katrina Bartas, May Hui

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(20), P. 3470 - 3485.e12

Published: Aug. 16, 2024

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as gatekeeper cocaine-induced behavioral plasticity. However, molecular and mechanisms underlying this function are unknown. Here, we show GPe parvalbumin-positive (GPe

Language: Английский

Citations

3
Regulation of hippocampal mossy fiber-CA3 synapse function by a Bcl11b/C1ql2/Nrxn3(25b+) pathway DOI Creative Commons
Artemis Koumoundourou,

Märt Rannap,

Elodie De Bruyckere

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Aug. 18, 2023

The transcription factor Bcl11b has been linked to neurodevelopmental and neuropsychiatric disorders associated with synaptic dysfunction. is highly expressed in dentate gyrus granule neurons required for the structural functional integrity of mossy fiber-CA3 synapses. underlying molecular mechanisms, however, remained unclear. We show mice that organizer molecule C1ql2 a direct target regulates vesicle recruitment long-term potentiation at synapses vivo vitro. Furthermore, we demonstrate exert its functions through interaction specific splice variant neurexin-3, Nrxn3(25b+). Interruption C1ql2-Nrxn3(25b+) by expression non-binding mutant or deletion Nrxn3 recapitulates major parts as well phenotype. Together, this study identifies novel C1ql2-Nrxn3(25b+)-dependent signaling pathway which controls synapse function. Thus, our findings contribute mechanistic understanding accompanied

Language: Английский

Citations

7
Regulation of hippocampal mossy fiber-CA3 synapse function by a Bcl11b/C1ql2/Nrxn3(25b+) pathway DOI Creative Commons
Artemis Koumoundourou,

Märt Rannap,

Elodie De Bruyckere

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 15, 2024

The transcription factor Bcl11b has been linked to neurodevelopmental and neuropsychiatric disorders associated with synaptic dysfunction. is highly expressed in dentate gyrus granule neurons required for the structural functional integrity of mossy fiber-CA3 synapses. underlying molecular mechanisms, however, remained unclear. We show mice that organizer molecule C1ql2 a direct target regulates vesicle recruitment long-term potentiation at synapses vivo vitro. Furthermore, we demonstrate exert its functions through interaction specific splice variant neurexin-3, Nrxn3(25b+). Interruption C1ql2-Nrxn3(25b+) by expression non-binding mutant or deletion Nrxn3 recapitulates major parts as well phenotype. Together, this study identifies novel C1ql2-Nrxn3(25b+)-dependent signaling pathway which controls synapse function. Thus, our findings contribute mechanistic understanding accompanied

Language: Английский

Citations

2