scholarly journals Functional analyses of pilin-like proteins from Francisella tularensis: complementation of type IV pilus phenotypes in Neisseria gonorrhoeae

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2546-2559 ◽  
Author(s):  
Emelie Salomonsson ◽  
Åke Forsberg ◽  
Norbert Roos ◽  
Claudia Holz ◽  
Berenike Maier ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Francisella Tularensis ◽  
Molecular Mechanisms ◽  
Indirect Evidence ◽  
Type Iv ◽  
Pilin Subunit ◽  
Surface Localization ◽  
Protein Secretion System ◽  
And Function ◽  
Functional Analyses

Accumulating evidence from a number of studies strongly suggests that proteins orthologous to those involved in type IV pili (Tfp) assembly and function are required for Francisella pathogenicity. However, the molecular mechanisms by which the components exert their influence on virulence remain poorly understood. Owing to the conservation and promiscuity of Tfp biogenesis machineries, expression of Tfp pilins in heterologous species has been used successfully to analyse organelle structure–function relationships. In this study we expressed a number of Francisella pilin genes in the Tfp-expressing pathogen Neisseria gonorrhoeae lacking its endogenous pilin subunit. Two gene products, the orthologous PilA proteins from Francisella tularensis subspecies tularensis and novicida, were capable of restoring the expression of Tfp-like appendages that were shown to be dependent upon the neisserial Tfp biogenesis machinery for surface localization. Expression of Francisella PilA pilins also partially restored competence for natural transformation in N. gonorrhoeae. This phenotype was not complemented by expression of the PulG and XcpT proteins, which are equivalent components of the related type II protein secretion system. Taken together, these findings provide compelling, although indirect, evidence of the potential for Francisella PilA proteins to express functional Tfp.

scholarly journals Type IV Pilus Assembly Proficiency and Dynamics Influence Pilin Subunit Phospho-Form Macro- and Microheterogeneity in Neisseria gonorrhoeae

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96419 ◽  
Author(s):  
Åshild Vik ◽  
Jan Haug Anonsen ◽  
Finn Erik Aas ◽  
Finn Terje Hegge ◽  
Norbert Roos ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Type Iv Pilus ◽  
Type Iv ◽  
Pilin Subunit ◽  
Pilus Assembly

scholarly journals Pseudomonas aeruginosa Type IV Pilus Expression in Neisseria gonorrhoeae: Effects of Pilin Subunit Composition on Function and Organelle Dynamics

2007 ◽  
Vol 189 (18) ◽  
pp. 6676-6685 ◽  
Author(s):  
Hanne C. Winther-Larsen ◽  
Matthew C. Wolfgang ◽  
Jos P. M. van Putten ◽  
Norbert Roos ◽  
Finn Erik Aas ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Neisseria Gonorrhoeae ◽  
Type Iv Pili ◽  
Type Iv ◽  
Pilin Subunit ◽  
Steady State Levels ◽  
Natural Genetic Transformation ◽  
Necessary And Sufficient ◽  
Pilin Protein ◽  
Behavior Sensitivity

ABSTRACT Type IV pili (TFP) play central roles in the expression of many phenotypes including motility, multicellular behavior, sensitivity to bacteriophages, natural genetic transformation, and adherence. In Neisseria gonorrhoeae, these properties require ancillary proteins that act in conjunction with TFP expression and influence organelle dynamics. Here, the intrinsic contributions of the pilin protein itself to TFP dynamics and associated phenotypes were examined by expressing the Pseudomonas aeruginosa PilAPAK pilin subunit in N. gonorrhoeae. We show here that, although PilAPAK pilin can be readily assembled into TFP in this background, steady-state levels of purifiable fibers are dramatically reduced relative those of endogenous pili. This defect is due to aberrant TFP dynamics as it is suppressed in the absence of the PilT pilus retraction ATPase. Functionally, PilAPAK pilin complements gonococcal adherence for human epithelial cells but only in a pilT background, and this property remains dependent on the coexpression of both the PilC adhesin and the PilV pilin-like protein. Since P. aeruginosa pilin only moderately supports neisserial sequence-specific transformation despite its assembly proficiency, these results together suggest that PilAPAK pilin functions suboptimally in this environment. This appears to be due to diminished compatibility with resident proteins essential for TFP function and dynamics. Despite this, PilAPAK pili support retractile force generation in this background equivalent to that reported for endogenous pili. Furthermore, PilAPAK pili are both necessary and sufficient for bacteriophage PO4 binding, although the strain remains phage resistant. Together, these findings have significant implications for TFP biology in both N. gonorrhoeae and P. aeruginosa.

scholarly journals NLRP3 maintains healthy pericytes in the brain

2019 ◽  
Author(s):  
Wenqiang Quan ◽  
Qinghua Luo ◽  
Qiqiang Tang ◽  
Tomomi Furihata ◽  
Dong Li ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Collagen Type Iv ◽  
Akt Inhibitor ◽  
Wild Type Littermate ◽  
Cerebral Microvessels ◽  
Protein Levels ◽  
Type Iv ◽  
Brain Pericytes ◽  
And Function ◽  
The Brain

Abstract Background Pericytes regulate structure and function of cerebral capillaries. Growing evidence shows that pericytes are damaged in the brain of Alzheimer’s disease (AD), which potentially contributes to AD pathogenesis. NLRP3-contained inflammasome is activated in AD brain and considered as a promising target for therapy. However, how NLRP3 affects brain pericytes is unclear. In our study, we investigated physiological function of NLRP3 in pericytes. Methods Immunohistological methods and Western blot were used to investigate pericytes and vasculature in the brains of 9-month-old NLRP3-deficient and wild-type littermate mice. Pericytes were also cultured and treated with NLRP3 inhibitor, recombinant IL-1β and AKT inhibitor. Then, proliferation, apoptosis and expression of PDGFRβ and CD13 in pericytes were analysed with biochemical methods. To investigate underlying molecular mechanisms, phosphorylation of protein kinases such as AKT, ERK and NF- k B were quantified. Results We observed that NLRP3 deficiency reduced the coverage of PDGFRβ-positive pericytes and collagen type IV-immunereactive vasculature in the brain. NLRP3 deficiency was also shown to decrease PDGFRβ and CD13 proteins in isolated cerebral microvessels. In cultured pericytes, inhibition of NLRP3 with MCC950 attenuated cell proliferation but did not induce apoptosis. NLRP3 inhibition also decreased protein levels of PDGFRβ and CD13. On the contrary, treatments with IL-1β increased protein levels of PDGFRβ and CD13 in pericytes. The alteration of PDGFRβ and CD13 protein levels was correlated with phosphorylation of AKT. Inhibition of AKT reduced PDGFRβ and CD13 in cultured pericytes. Conclusions NLRP3 might be essential to maintain healthy pericytes in the brain through activating AKT. Adverse effects on brain pericytes should be considered in the possible clinical therapies with NLRP3 inhibitors.

A Mucin-Specific Protease Enables Molecular and Functional Analysis of Human Cancer-Associated Mucins

2018 ◽  
Author(s):  
Stacy A. Malaker ◽  
Kayvon Pedram ◽  
Michael J. Ferracane ◽  
Elliot C. Woods ◽  
Jessica Kramer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Mechanisms ◽  
Cultured Cells ◽  
High Resolution Mass Spectrometry ◽  
Human Cancer ◽  
Glycosylation Sites ◽  
Bacterial Protease ◽  
Specific Protease ◽  
To Come ◽  
And Function

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>

scholarly journals Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mechanical Forces ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Development ◽  
And Function ◽  
The Impact

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

scholarly journals Emerging Data on the Diversity of Molecular Mechanisms Involving C/D snoRNAs

2021 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
Laeya Baldini ◽  
Bruno Charpentier ◽  
Stéphane Labialle
Keyword(s):  
Ribosomal Rna ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Accurate Description ◽  
Small Nucleolar Rnas ◽  
Age Of Maturity ◽  
Non Coding Rnas ◽  
And Function ◽  
Nucleolar Rnas

Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Expression and function of Smad7 in autoimmune and inflammatory diseases

2021 ◽  
Author(s):  
Yiping Hu ◽  
Juan He ◽  
Lianhua He ◽  
Bihua Xu ◽  
Qingwen Wang
Keyword(s):  
Posttranscriptional Regulation ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Kidney Diseases ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Negative Regulator ◽  
Signaling Mechanism ◽  
And Function

AbstractTransforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.

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