Cluster nanoarchitecture and structural diversity of PIEZO1 in intact cells DOI Creative Commons
Clément Verkest,

Lucas Roettger,

Nadja Zeitzschel

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 28, 2024

Abstract The mechanically activated ion channel PIEZO1 confers mechanosensitivity to many cell types and is thus essential for numerous physiological processes triggered by mechanical cues 1–4 . channels assemble as propeller-shaped trimers 5–7 , which supposedly undergo a transition from curved conformational state into flattened upon activation 8–11 Whether this gating model also applies clusters what extent membrane curvature alters conformation in living cells, is, however, still unclear. Here, we used MINFLUX nanoscopy resolve the architecture of demonstrate that collectively deform pit-shaped invaginations, accommodate multiple flatten response stimulation. Moreover, our data suggests deformability sensitivity are altered rigidity cytoskeleton. Together, provide previously unrecognized structural details about subcellular distribution variability different cellular compartments, challenge proposed hypotheses derived studies isolated highlight importance examining its native environment, where additional factors contribute function structure.

Язык: Английский

Membrane curvature governs the distribution of Piezo1 in live cells DOI Creative Commons
Shilong Yang,

Xinwen Miao,

Steven E. Arnold

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Дек. 3, 2022

Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of within cell essential for various biological processes including cytokinesis, migration, and wound healing. However, the underlying principles that guide subcellular remain largely unexplored. Here, we demonstrate membrane curvature serves as key regulator spatial plasma living depletes from highly curved protrusions such filopodia enriches to nanoscale invaginations. Quantification curvature-dependent sorting directly reveals situ nano-geometry Piezo1-membrane complex. density on increases upon activation, independent calcium, suggesting flattening opening. Consequently, expression inhibits formation, an effect diminishes with activation.

Язык: Английский

Процитировано

51
Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching DOI Creative Commons

Chuanyun Xu,

Zhuoran Li, Cheng Lyu

и другие.

Cell, Год журнала: 2024, Номер 187(18), С. 5081 - 5101.e19

Опубликована: Июль 11, 2024

In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use situ proximity labeling to obtain the interactome of a teneurin (Ten-m) Drosophila brain. Genetic interaction studies using quantitative matching assays both olfactory receptor neurons (ORNs) and projection (PNs) reveal common pathway: Ten-m binds negatively regulates RhoGAP, thus activating Rac1 small GTPases promote Developmental analyses with single-axon resolution identify cellular mechanism matching: promotes local F-actin levels stabilizes ORN axon branches contact PN dendrites. Combining spatial proteomics high-resolution phenotypic analyses, this study advanced our understanding molecular mechanisms

Язык: Английский

Процитировано

10
Spatiotemporally resolved mapping of extracellular proteomes via in vivo-compatible TyroID DOI Creative Commons
Zijuan Zhang, Yankun Wang,

Wenjie Lu

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 15, 2025

Extracellular proteins play pivotal roles in both intracellular signaling and intercellular communications health disease. While recent advancements proximity labeling (PL) methods, such as peroxidase- photocatalyst-based approaches, have facilitated the resolution of extracellular proteomes, their vivo compatibility remains limited. Here, we report TyroID, an vivo-compatible PL method for unbiased mapping with high spatiotemporal resolution. TyroID employs plant- bacteria-derived tyrosinases to produce reactive o-quinone intermediates, enabling multiple residues on endogenous bioorthogonal handles, thereby allowing identification via chemical proteomics. We validate TyroID's specificity by proteomes HER2-neighboring using affibody-directed recombinant tyrosinases. Demonstrating its superiority over other enables including HER2-proximal tumor xenografts, quantifying turnover plasma hippocampal-specific live mouse brains. emerges a potent tool investigating protein localization molecular interactions within living organisms. is that maps through efficiently labels study interactions.

Язык: Английский

Процитировано

2
In situ cell-type-specific cell-surface proteomic profiling in mice DOI Creative Commons

S. Andrew Shuster,

Jun Li, Uree Chon

и другие.

Neuron, Год журнала: 2022, Номер 110(23), С. 3882 - 3896.e9

Опубликована: Окт. 10, 2022

Cell-surface proteins (CSPs) mediate intercellular communication throughout the lives of multicellular organisms. However, there are no generalizable methods for quantitative CSP profiling in specific cell types vertebrate tissues. Here, we present situ cell-surface proteome extraction by extracellular labeling (iPEEL), a proximity method mice that enables spatiotemporally precise proteomes cell-type-specific environment native tissues discovery proteomics. Applying iPEEL to developing and mature cerebellar Purkinje cells revealed differential enrichment CSPs with post-translational protein processing synaptic functions proteomes, respectively. A proteome-instructed vivo loss-of-function screen identified critical, multifaceted role Armh4 dendrite morphogenesis. overexpression also disrupts morphogenesis; this effect requires its conserved cytoplasmic domain is augmented disrupting endocytosis. Our results highlight utility mammalian identifying regulators signaling.

Язык: Английский

Процитировано

37
Synaptic promiscuity in brain development DOI Creative Commons
Neele Wolterhoff, P. Robin Hiesinger

Current Biology, Год журнала: 2024, Номер 34(3), С. R102 - R116

Опубликована: Фев. 1, 2024

Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out their developmental context, readily form unspecific synapses. How does genome encode brain wiring in light this apparent contradiction? Synaptic specificity outcome long series processes and mechanisms before, during after synapse formation. much promiscuity permissible or necessary at moment partner choice depends on extent to which prior development restricts available partners subsequent corrects initially made can thereby play important roles precise connectivity, but also facilitate flexibility robustness. In review, we assess experimental evidence prevalence promiscuous formation development. Many well-established approaches are based genetic perturbation an assessment only adult; make it difficult pinpoint when given defect mechanism occurred. many cases, such studies reveal that restrict availability already Subsequently, choice, factors including competency, interaction dynamics molecular recognition further partners. The discussion through lens suggests algorithmic process neurons capable continuously prevented from making wrong choices, with no single time point sufficient explain outcome.

Язык: Английский

Процитировано

8
Drosophila olfaction: past, present and future DOI Creative Commons
Richard Benton

Proceedings of the Royal Society B Biological Sciences, Год журнала: 2022, Номер 289(1989)

Опубликована: Дек. 14, 2022

Among the many wonders of nature, sense smell fly Drosophila melanogaster might seem, at first glance, esoteric interest. Nevertheless, for over a century, ‘nose’ this insect has been an extraordinary system to explore questions in animal behaviour, ecology and evolution, neuroscience, physiology molecular genetics. The insights gained are relevant our understanding sensory biology vertebrates, including humans, other species, encompassing those detrimental human health. Here, I present overview current knowledge D. olfaction, from molecules behaviours, with emphasis on historical motivations studies illustration how technical innovations have enabled advances. also highlight some pressing long-term questions.

Язык: Английский

Процитировано

28
Origin of wiring specificity in an olfactory map revealed by neuron type–specific, time-lapse imaging of dendrite targeting DOI Creative Commons

Kenneth Kin Lam Wong,

Tongchao Li, Tian-Ming Fu

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Март 28, 2023

How does wiring specificity of neural maps emerge during development? Formation the adult Drosophila olfactory glomerular map begins with patterning projection neuron (PN) dendrites at early pupal stage. To better understand origin this map, we created genetic tools to systematically characterize dendrite across development PN type–specific resolution. We find that PNs use lineage and birth order combinatorially build initial dendritic map. Specifically, directs targeting in rotating binary manners for anterodorsal lateral lineages, respectively. Two-photon– adaptive optical lattice light-sheet microscope–based time-lapse imaging reveals initiate active direction-dependent branch stabilization on timescale seconds. Moreover, are used both larval circuits prune their larval-specific re-extend new simultaneously facilitate timely organization. Our work highlights power necessity type-specific neuronal access identifying mechanisms underlie complex patterns functional maps.

Язык: Английский

Процитировано

12
Development and function of the medial amygdala DOI
Nandkishore Prakash,

Ameair Abu Irqeba,

Jackie D. Corbin

и другие.

Trends in Neurosciences, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

5
Cytokine storm-calming property of the isoquinoline alkaloids in Coptis chinensis Franch DOI Creative Commons
Yuejia Lan, Huan Wang, Jiasi Wu

и другие.

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Сен. 6, 2022

Coronavirus disease (COVID-19) has spread worldwide and its effects have been more devastating than any other infectious disease. Importantly, patients with severe COVID-19 show conspicuous increases in cytokines, including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, tumor necrosis factor (TNF)-α, IL-1, IL-18, IL-17, characteristics of the cytokine storm (CS). Although recently studied inhibitors are considered as potent targeted approaches, once an immunological complication like CS happens, anti-viral or anti-inflammation based monotherapy alone is not enough. Interestingly, certain isoquinoline alkaloids Coptis chinensis Franch. (CCFIAs) exerted a multitude biological activities such anti-inflammatory, antioxidant, antibacterial, immunomodulatory etc, revealing great potential for calming CS. Therefore, this timeline review, we report compare CCFIAs to attenuate exacerbation inflammatory responses by modulating signaling pathways NF-ĸB, mitogen-activated kinase, JAK/STAT, NLRP3. In addition, also discuss role berberine (BBR) two different triggers CS, namely sepsis viral infections, well clinical applications. These evidence provide rationale considering therapeutic agents against suggestion requires further validation studies.

Язык: Английский

Процитировано

15
Understanding the molecular diversity of synapses DOI
Marc van Oostrum, Beatriz Álvarez-Castelao

Nature reviews. Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Язык: Английский

Процитировано

3