Trans-synaptic molecular context of NMDA receptor nanodomains DOI Creative Commons
Michael Anderson, Poorna A. Dharmasri, Martina Damenti

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 23, 2023

Tight coordination of the spatial relationships between protein complexes is required for cellular function. In neuronal synapses, many proteins responsible neurotransmission organize into subsynaptic nanoclusters whose trans-cellular alignment modulates synaptic signal propagation. However, these and NMDA receptors (NMDARs), which are learning memory, remain undefined. Here, we mapped relationship key NMDAR subunits to reference in active zone postsynaptic density using multiplexed super-resolution DNA-PAINT microscopy. GluN2A GluN2B formed with diverse configurations that, surprisingly, were not localized near presynaptic vesicle release sites marked by Munc13-1. a subset was configured maintain activation: internally denser, aligned abundant PSD-95, associated closely specific nanodomains. This work reveals new principle regulating signaling suggests that functional architecture depends on assembly multiprotein nanodomains interior construction conditional relationships.

Язык: Английский

Live imaging of paracrine signaling: Advances in visualization and tracking techniques DOI Creative Commons

Eriko Deguchi,

Michiyuki Matsuda, Kenta Terai

и другие.

Cell Structure and Function, Год журнала: 2025, Номер 50(1), С. 1 - 14

Опубликована: Янв. 1, 2025

Live imaging techniques have revolutionized our understanding of paracrine signaling, a crucial form cell-to-cell communication in biological processes. This review examines recent advances visualizing and tracking factors through four key stages: secretion from producing cells, diffusion extracellular space, binding to target activation intracellular signaling within cells. Paracrine factor can be directly visualized by fluorescent protein tagging ligand, or indirectly the cleavage transmembrane pro-ligands plasma membrane fusion endosomes comprising factors. Diffusion has been studied using such as fluorescence correlation spectroscopy (FCS), recovery after photobleaching (FRAP), decay photoactivation (FDAP), single-molecule tracking. Binding cells various biosensors, including GPCR-activation-based (GRAB) sensors Förster resonance energy transfer (FRET) probes for receptor tyrosine kinases. Finally, is monitored biosensors second messengers, transcription factors, so on. In addition tools, also highlights emerging optogenetic chemogenetic tools triggering release which essential associating outcomes during bioimaging signaling.Key words: live imaging, optogenetics, chemogenetics.

Язык: Английский

Процитировано

0

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

и другие.

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Role of astroglia and microglia in Alzheimer's disease and multiple therapeutic interventions DOI
Lei Li, Ying Wang,

Qilin Feng

и другие.

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Июнь 2, 2025

Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) formed aggregates hyperphosphorylated tau proteins. It presents a formidable global health challenge, prompting the exploration innovative therapeutic strategies. This review aims to provide thorough discussion astrocytes microglia examine whether they are overall beneficial or detrimental for AD on level. Based this, this describes treatment solutions that likely entail manipulation glial cells reduce inflammation, opting boost clearance toxic proteins, thus stabilizing effects AD. These entities, inherent central nervous system, extend their functions beyond structural support, actively engaging in various physiological pathological processes associated with Both astroglia contribute significantly neuroinflammatory response observed Reactive release inflammatory mediators, while activated cytokines, chemokines, reactive oxygen species, collectively assisting chronic state neuroinflammation. Additionally, partake Aβ, play pivotal role phagocytosing Aβ plaques. In AD, ongoing inflammation may cause buildup which causes problems also worsens these issues communication between neurons, key factor cognitive decline. addition, there tremendous opportunities identify new biomarkers specific disorders, genomic epigenomic approaches selection patients, using multimodal imaging techniques, application machine learning algorithms future personalized glial-targeted therapies.

Язык: Английский

Процитировано

0

Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity DOI Creative Commons
Theresa M. Welle, Katharine R. Smith

Current Opinion in Neurobiology, Год журнала: 2024, Номер 90, С. 102952 - 102952

Опубликована: Дек. 25, 2024

Язык: Английский

Процитировано

2

Trans-synaptic molecular context of NMDA receptor nanodomains DOI Creative Commons
Michael Anderson, Poorna A. Dharmasri, Martina Damenti

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 23, 2023

Tight coordination of the spatial relationships between protein complexes is required for cellular function. In neuronal synapses, many proteins responsible neurotransmission organize into subsynaptic nanoclusters whose trans-cellular alignment modulates synaptic signal propagation. However, these and NMDA receptors (NMDARs), which are learning memory, remain undefined. Here, we mapped relationship key NMDAR subunits to reference in active zone postsynaptic density using multiplexed super-resolution DNA-PAINT microscopy. GluN2A GluN2B formed with diverse configurations that, surprisingly, were not localized near presynaptic vesicle release sites marked by Munc13-1. a subset was configured maintain activation: internally denser, aligned abundant PSD-95, associated closely specific nanodomains. This work reveals new principle regulating signaling suggests that functional architecture depends on assembly multiprotein nanodomains interior construction conditional relationships.

Язык: Английский

Процитировано

3