Novel Functions of the Septin Cytoskeleton

Ivanov, Andrei I.; Le, Hongnga T.; Naydenov, Nayden G.; Rieder, Florian

doi:10.1016/j.ajpath.2020.09.007

Cited by 30 publications

(11 citation statements)

References 115 publications

(176 reference statements)

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“…The human septin family contains 14 genes (SEPT1-SEPT14), encoding dozens of different septin proteins. Among them, SEPT9 encodes a GTP-binding protein, which plays a role in cytokinesis, intracellular material transport, cell cycle regulation, and apoptosis ( Ivanov et al, 2021 ). Wu et al (2017) found that SEPT9 is hypermethylated in TGF-β1-treated mouse HSCs and CCl 4 -treated mouse liver, and SEPT9 protein expression is significantly reduced, leading to increased ECM accumulation and aggravated fibrosis compared with that in controls.…”

Section: Liver Fibrosis-related Genes and Dna Methylationmentioning

confidence: 99%

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

et al. 2023

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Liver fibrosis is a repair response to injury caused by various chronic stimuli that continually act on the liver. Among them, the activation of hepatic stellate cells (HSCs) and their transformation into a myofibroblast phenotype is a key event leading to liver fibrosis, however the mechanism has not yet been elucidated. The molecular basis of HSC activation involves changes in the regulation of gene expression without changes in the genome sequence, namely, via epigenetic regulation. DNA methylation is a key focus of epigenetic research, as it affects the expression of fibrosis-related, metabolism-related, and tumor suppressor genes. Increasing studies have shown that DNA methylation is closely related to several physiological and pathological processes including HSC activation and liver fibrosis. This review aimed to discuss the mechanism of DNA methylation in the pathogenesis of liver fibrosis, explore DNA methylation inhibitors as potential therapies for liver fibrosis, and provide new insights on the prevention and clinical treatment of liver fibrosis.

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Section: Liver Fibrosis-related Genes and Dna Methylationmentioning

confidence: 99%

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

et al. 2023

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“…This analysis uncovered several plasma proteins significantly associated with combined asthma‐atopy phenotypes but not with asthma overall, including septin‐6 (SEPT6). Septins play a crucial role in inflammation and have potential in therapeutic treatments 64 …”

Section: Discussionmentioning

confidence: 99%

“…Septins play a crucial role in inflammation and have potential in therapeutic treatments. 64 A recent study of asthma genetics implicated 174 genes. 65 Of these, one (IL4R) was associated with asthma in our data.…”

Section: Discussionmentioning

confidence: 99%

Plasma protein signatures of adult asthma

Smilnak,

Lee,

Chattopadhyay

et al. 2024

Allergy

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BackgroundAdult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.MethodsProtein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non‐case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non‐case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta‐analyzed using inverse‐variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with atopy (n = 207), asthma without atopy (n = 554), atopy without asthma (n = 147), compared to neither (n = 948)).ResultsMeta‐analysis of 4860 proteins identified 115 significantly (FDR<0.05) associated with asthma. Multiple signaling pathways related to airway inflammation and pulmonary injury were enriched (FDR<0.05) among these proteins. A proteomic score generated using machine learning provided predictive value for asthma (AUC = 0.77, 95% CI = 0.75–0.79 in training set; AUC = 0.72, 95% CI = 0.69–0.75 in validation set). Twenty proteins are targeted by approved or investigational drugs for asthma or other conditions, suggesting potential drug repurposing. The combined asthma‐atopy phenotype showed significant associations with 20 proteins, including five not identified in the overall asthma analysis.ConclusionThis first large‐scale proteomics study identified over 100 plasma proteins associated with current asthma in adults. In addition to validating previous associations, we identified many novel proteins that could inform development of diagnostic biomarkers and therapeutic targets in asthma management.

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“…The main challenge of studying the septin’s biology is the complexity of septins. In mammals, there are 13 septin genes and at least 11 pseudogenes, coding for transcripts and proteins with extensive posttranscriptional modifications and alternative splicing isoforms ( 14 ). Moreover, septin’s biology is very complex because septins are evolutionary old and present in divergent eukaryotic lineages, including algae and ciliates ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Septins provide microenvironment sensing and cortical actomyosin partitioning in motile amoeboid T lymphocytes

Zhovmer,

Manning,

Smith

et al. 2024

Sci. Adv.

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The all-terrain motility of lymphocytes in tissues and tissue-like gels is best described as amoeboid motility. For amoeboid motility, lymphocytes do not require specific biochemical or structural modifications to the surrounding extracellular matrix. Instead, they rely on changing shape and steric interactions with the microenvironment. However, the exact mechanism of amoeboid motility remains elusive. Here, we report that septins participate in amoeboid motility of T cells, enabling the formation of F-actin and α-actinin–rich cortical rings at the sites of cell cortex–indenting collisions with the extracellular matrix. Cortical rings compartmentalize cells into chains of spherical segments that are spatially conformed to the available lumens, forming transient “hourglass”-shaped steric locks onto the surrounding collagen fibers. The steric lock facilitates pressure-driven peristaltic propulsion of cytosolic content by individually contracting cell segments. Our results suggest that septins provide microenvironment-guided partitioning of actomyosin contractility and steric pivots required for amoeboid motility of T cells in tissue-like microenvironments.

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Novel Functions of the Septin Cytoskeleton

Cited by 30 publications

References 115 publications

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

Plasma protein signatures of adult asthma

Septins provide microenvironment sensing and cortical actomyosin partitioning in motile amoeboid T lymphocytes

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