Septins as membrane influencers: direct play or in association with other cytoskeleton partners

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 17, 2023

The cytoskeleton comprises three polymerizing structures that have been studied for a long time, actin microfilaments, microtubules and intermediate filaments, plus more recently investigated dynamic assemblies like septins or the endocytic-sorting complex required transport (ESCRT) complex. These filament-forming proteins control several cell functions through crosstalks with each other membranes. In this review, we report recent works address how bind to membranes, influence their shaping, organization, properties functions, either by binding them directly indirectly elements.

Language: Английский

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Molecular mechanisms of Ustilaginoidea virens pathogenicity and their utilization in disease control

Phytopathology Research, Journal Year: 2023, Volume and Issue: 5(1)

Published: May 9, 2023

Abstract Rice false smut, caused by Ustilaginoidea virens , is one of the most important diseases in rice. The disease not only causes significant yield losses China and worldwide but also produces multiple types mycotoxins that pose a serious threat to health humans animals. To effectively prevent control disease, pathogenicity mechanisms U. have been studied preliminarily, some strategies developed. This review focuses on recent progress understanding molecular pathogenicity, including virulence-related genes, transcriptional regulation virulence effector-mediated interactions between rice . Based underlying rice- interactions, possibilities genes host immune-related as potential targets for biological agents, host-induced gene silencing, design breeding are discussed.

Language: Английский

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Targeting autophagy impairment improves the phenotype of a novel CLN8 zebrafish model

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 197, P. 106536 - 106536

Published: May 17, 2024

CLN8 is an endoplasmic reticulum cargo receptor and a regulator of lysosome biogenesis whose loss function leads to neuronal ceroid lipofuscinosis. has been linked autophagy lipid metabolism, but much remains be learned, there are no therapies acting on the molecular signatures in this disorder. The present study aims characterize pathways involved disease and, by pinpointing altered ones, identify potential therapies. To bridge gap between cell mammalian models, we generated new zebrafish model deficiency, which recapitulates pathological features disease. We observed, for first time, that dysfunction impairs autophagy. Using modulators, showed trehalose SG2 able attenuate phenotype mutant larvae, confirming impairment as secondary event progression. Overall, our successful modeling defects highlights novel vivo model's strong instrument exploring role cellular pathways, with view identifying small molecules treat rare

Language: Английский

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Septin 3 regulates memory and L-LTP-dependent extension of endoplasmic reticulum into spines

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115352 - 115352

Published: Feb. 1, 2025

Transient memories are converted to persistent at the synapse and circuit/systems levels. The synapse-level consolidation parallels electrophysiological transition from early- late-phase long-term potentiation of synaptic transmission (E-/L-LTP). While glutamate signaling upregulations coupled with dendritic spine enlargement common underpinnings E-LTP L-LTP, mechanisms conferring persistence on L-LTP remain unclear. Here, we show that induced perforant path-hippocampal dentate gyrus (DG) synapses accompanies cytoskeletal remodeling involves actin septin subunit SEPT3. in DG neurons causes fast enlargement, followed by SEPT3-dependent smooth endoplasmic reticulum (sER) extension into enlarged spines. Spines containing sER greater Ca2+ responses upon input local activity. Consistently, Sept3 knockout mice (Sept3-/-) impairs memory a scarcity sER-containing These findings indicate concept active spines serves as basis consolidation.

Language: Английский

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Microscale thermophoresis (MST) and spectral shift (SpS) in drug discovery

TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 176, P. 117716 - 117716

Published: April 16, 2024

Language: Английский

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Septins and K63 ubiquitin chains are present in separate bacterial microdomains during autophagy of entrapped Shigella

Journal of Cell Science, Journal Year: 2023, Volume and Issue: 136(7)

Published: March 20, 2023

ABSTRACT During host cell invasion, Shigella escapes to the cytosol and polymerizes actin for cell-to-cell spread. To restrict spread, cells employ cell-autonomous immune responses including antibacterial autophagy septin cage entrapment. How septins interact with process target destruction is poorly understood. Here, we employed a correlative light cryo-soft X-ray tomography (cryo-SXT) pipeline study entrapment in its near-native state. Quantitative cryo-SXT showed that fragments mitochondria enabled visualization of X-ray-dense structures (∼30 nm resolution) surrounding entrapped cages. Using Airyscan confocal microscopy, observed lysine 63 (K63)-linked ubiquitin chains decorating septin-cage-entrapped Shigella. Remarkably, K63 are present separate bacterial microdomains, indicating they recruited separately during autophagy. Cryo-SXT live-cell imaging revealed an interaction between LC3B-positive membranes Together, these findings demonstrate how septin-caged targeted provide fundamental insights into autophagy–cytoskeleton interactions.

Language: Английский

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SEPT3 as a Potential Molecular Target of Triple-Negative Breast Cancer

International Journal of General Medicine, Journal Year: 2024, Volume and Issue: Volume 17, P. 1605 - 1613

Published: April 1, 2024

The survival rate for triple-negative breast cancer (TNBC) is very low due to its advanced metastatic and aggressive nature, there no specific target improve the rate. expression clinical signature of neuronal-specific septin-3 (Septin3, SEPT3) in TNBC remain undetermined.

Language: Английский

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Simultaneous co‐overexpression of Saccharomyces cerevisiae septins Cdc3 and Cdc10 drives pervasive, phospholipid‐, and tag‐dependent plasma membrane localization

Cytoskeleton, Journal Year: 2023, Volume and Issue: 80(7-8), P. 199 - 214

Published: April 26, 2023

Abstract Septin proteins contribute to many eukaryotic processes involving cellular membranes. In the budding yeast Saccharomyces cerevisiae , septin hetero‐oligomers interact with plasma membrane (PM) almost exclusively at future site of cytokinesis. While multiple mechanisms recruitment have been identified, including direct interactions specific phospholipids and curvature‐sensitive via amphipathic helices, these do not fully explain why septins localize all over inner leaflet PM. engineering an inducible split‐yellow fluorescent protein (YFP) system measure kinetics complex assembly, we found that ectopic co‐overexpression two tagged septins, Cdc3 Cdc10, resulted in nearly uniform PM localization, as well perturbation endogenous function. localization function gametogenesis were also perturbed. required C‐terminal YFP fragment fused C terminus Cdc3, septin‐associated kinases Cla4 Gin4, phosphotidylinositol‐4,5‐bis‐phosphate (PI[4,5]P 2 ), but putative PI(4,5)P ‐binding residues Cdc3. Endogenous Cdc10 was recruited PM, likely contributing functional interference. PM‐localized did exchange cytosolic pool, indicative stable polymers. These findings provide new clues what normally restricts

Language: Английский

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The Small-Molecule Enhancers of Autophagy AUTEN-67 and -99 Delay Ageing in Drosophila Striated Muscle Cells

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8100 - 8100

Published: April 30, 2023

Autophagy (cellular self-degradation) plays a major role in maintaining the functional integrity (homeostasis) of essentially all eukaryotic cells. During process, superfluous and damaged cellular constituents are delivered into lysosomal compartment for enzymatic degradation. In humans, age-related defects autophagy have been linked to incidence various age-associated degenerative pathologies (e.g., cancer, neurodegenerative diseases, diabetes, tissue atrophy fibrosis, immune deficiency) accelerated ageing. Muscle mass decreases at detectable levels already middle-aged patients, this change can increase up 30-50% age 80. AUTEN-67 -99, two small-molecule enhancers with cytoprotective anti-ageing effects previously identified initially characterized. These compounds life span wild-type model strains fruit fly Drosophila melanogaster. Adult flies were treated these AUTEN molecules via feeding. Fluorescence electron microscopy Western blotting used assess level senescence. Flying tests measure locomotor ability animals different ages. current study, -99 observed on striated muscle cells using indirect flight (IFM) as model. The capable inducing IFM cells, thereby lowering accumulation protein aggregates mitochondria, both characterizing Furthermore, significantly improved flying animals. decrease rate which age. results may significant medical relevance that could be further examined mammalian models.

Language: Английский

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Smoking during pregnancy is associated with the placental proteome

Reproductive Toxicology, Journal Year: 2023, Volume and Issue: 119, P. 108409 - 108409

Published: May 18, 2023

Maternal smoking during pregnancy (MSDP) is a significant risk factor for the development of foetal, neonatal, and childhood morbidities. We hypothesized that infants exposed to MSDP have distinct proteomic expression in their term placentas compared without such an exposure. A total 39 (cord blood cotinine levels >1 ng/ml) 44 not were included study. Women with chronic disease, body mass index >30, or history uterine surgery excluded. Total proteome abundance was analysed quantitative spectrometry. For univariate analysis differences placental protein between groups, ANOVA multiple testing corrections by Benjamini–Hochberg method used. multivariate analysis, we used principal component partial least squares, lasso, random forest, neural networks. The analyses showed four differentially abundant proteins (PXDN, CYP1A1, GPR183, KRT81) when heavy moderate groups non-smokers. With help machine learning, found additional six (SEPTIN3, CRAT, NAAA, CD248, CADM3, ZNF648) discriminants MSDP. these ten together explained 74.1% variation cord (p = 0.002). Infants differential placentas. report several first time setting believe findings supplement current understanding how affects proteome.

Language: Английский

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