scholarly journals The lysosomal Ragulator complex plays an essential role in leukocyte trafficking by activating myosin II

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Takeshi Nakatani ◽  
Kohei Tsujimoto ◽  
JeongHoon Park ◽  
Tatsunori Jo ◽  
Tetsuya Kimura ◽  
...  
Keyword(s):  
Immune Responses ◽  
Essential Role ◽  
Myosin Ii ◽  
Nutrient Sensing ◽  
Leukocyte Migration ◽  
Interacting Protein ◽  
Mechanistic Target Of Rapamycin ◽  
Motile Cells ◽  
A Subunit ◽  
Actomyosin Contraction

AbstractLysosomes are involved in nutrient sensing via the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 is tethered to lysosomes by the Ragulator complex, a heteropentamer in which Lamtor1 wraps around Lamtor2–5. Although the Ragulator complex is required for cell migration, the mechanisms by which it participates in cell motility remain unknown. Here, we show that lysosomes move to the uropod in motile cells, providing the platform where Lamtor1 interacts with the myosin phosphatase Rho-interacting protein (MPRIP) independently of mTORC1 and interferes with the interaction between MPRIP and MYPT1, a subunit of myosin light chain phosphatase (MLCP), thereby increasing myosin II–mediated actomyosin contraction. Additionally, formation of the complete Ragulator complex is required for leukocyte migration and pathophysiological immune responses. Together, our findings demonstrate that the lysosomal Ragulator complex plays an essential role in leukocyte migration by activating myosin II through interacting with MPRIP.

scholarly journals Contribution of Filopodia to Cell Migration: A Mechanical Link between Protrusion and Contraction

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Fei Xue ◽  
Deanna M. Janzen ◽  
David A. Knecht
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Myosin Ii ◽  
Temporal Distribution ◽  
Leading Edge ◽  
Distal Portion ◽  
Actin Binding ◽  
Actin Networks ◽  
Motile Cells ◽  
A Cell

Numerous F-actin containing structures are involved in regulating protrusion of membrane at the leading edge of motile cells. We have investigated the structure and dynamics of filopodia as they relate to events at the leading edge and the function of the trailing actin networks. We have found that although filopodia contain parallel bundles of actin, they contain a surprisingly nonuniform spatial and temporal distribution of actin binding proteins. Along the length of the actin filaments in a single filopodium, the most distal portion contains primarily T-plastin, while the proximal portion is primarily bound byα-actinin and coronin. Some filopodia are stationary, but lateral filopodia move with respect to the leading edge. They appear to form a mechanical link between the actin polymerization network at the front of the cell and the myosin motor activity in the cell body. The direction of lateral filopodial movement is associated with the direction of cell migration. When lateral filopodia initiate from and move toward only one side of a cell, the cell will turn opposite to the direction of filopodial flow. Therefore, this filopodia-myosin II system allows actin polymerization driven protrusion forces and myosin II mediated contractile force to be mechanically coordinated.

scholarly journals A Peptidoglycan-Remodeling Enzyme Is Critical for Bacteroid Differentiation in Bradyrhizobium spp. During Legume Symbiosis

2016 ◽  
Vol 29 (6) ◽  
pp. 447-457 ◽  
Author(s):  
Djamel Gully ◽  
Daniel Gargani ◽  
Katia Bonaldi ◽  
Cédric Grangeteau ◽  
Clémence Chaintreuil ◽  
...  
Keyword(s):  
Immune Responses ◽  
Essential Role ◽  
Morphological Changes ◽  
Large Fraction ◽  
Morphological Differentiation ◽  
Capsular Polysaccharides ◽  
Cell Enlargement ◽  
Legume Symbiosis ◽  
Bradyrhizobium Spp ◽  
Peptidoglycan Layer

In response to the presence of compatible rhizobium bacteria, legumes form symbiotic organs called nodules on their roots. These nodules house nitrogen-fixing bacteroids that are a differentiated form of the rhizobium bacteria. In some legumes, the bacteroid differentiation comprises a dramatic cell enlargement, polyploidization, and other morphological changes. Here, we demonstrate that a peptidoglycan-modifying enzyme in Bradyrhizobium strains, a DD-carboxypeptidase that contains a peptidoglycan-binding SPOR domain, is essential for normal bacteroid differentiation in Aeschynomene species. The corresponding mutants formed bacteroids that are malformed and hypertrophied. However, in soybean, a plant that does not induce morphological differentiation of its symbiont, the mutation does not affect the bacteroids. Remarkably, the mutation also leads to necrosis in a large fraction of the Aeschynomene nodules, indicating that a normally formed peptidoglycan layer is essential for avoiding the induction of plant immune responses by the invading bacteria. In addition to exopolysaccharides, capsular polysaccharides, and lipopolysaccharides, whose role during symbiosis is well defined, our work demonstrates an essential role in symbiosis for yet another rhizobial envelope component, the peptidoglycan layer.

scholarly journals Pathogenesis of Fungal and Bacterial Microbes

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 602
Author(s):  
Jennifer Geddes-McAlister
Keyword(s):  
Immune Responses ◽  
Defense Responses ◽  
Nutrient Sensing ◽  
Microbial Pathogenesis ◽  
Special Issue ◽  
Microbial Structures ◽  
Complex Process ◽  
Host Status ◽  
Pathogenic Microbes ◽  
Insight Into

The pathogenesis of fungal and bacterial microbes is a complex process involving distinct parameters, including virulence factors, nutrient sensing and availability, microbial signals, as well as host status and defense responses. Defining pathogenesis improves our understanding of how an organism causes diseases and provides insight into novel prospects to combat infection. The effects of pathogenic microbes have significant impact on diverse sectors, including health, agriculture, and economics, underscoring their immense importance in society. Articles in this Special Issue address unique aspects of microbial pathogenesis by exploring interactions between host and pathogen during infection, defining inflammatory immune responses, profiling the importance of essential microbial structures associated with virulence, and outlining critical considerations driving complex diseases.

scholarly journals An Essential Role for SNX1 in Lysosomal Sorting of Protease-activated Receptor-1: Evidence for Retromer-, Hrs-, and Tsg101-independent Functions of Sorting Nexins

2006 ◽  
Vol 17 (3) ◽  
pp. 1228-1238 ◽  
Author(s):  
Anuradha Gullapalli ◽  
Breann L. Wolfe ◽  
Courtney T. Griffin ◽  
Terry Magnuson ◽  
JoAnn Trejo
Keyword(s):  
Essential Role ◽  
Resistant Mutant ◽  
Interacting Protein ◽  
Sorting Nexins ◽  
Surface Receptors ◽  
Endosomal Membrane ◽  
Independent Functions ◽  
Lysosomal Sorting ◽  
Protease Activated Receptor 1 ◽  
In Cells

Sorting nexin 1 (SNX1) and SNX2 are the mammalian homologues of the yeast Vps5p retromer component that functions in endosome-to-Golgi trafficking. SNX1 is also implicated in endosome-to-lysosome sorting of cell surface receptors, although its requirement in this process remains to be determined. To assess SNX1 function in endocytic sorting of protease-activated receptor-1 (PAR1), we used siRNA to deplete HeLa cells of endogenous SNX1 protein. PAR1, a G-protein-coupled receptor, is proteolytically activated by thrombin, internalized, sorted predominantly to lysosomes, and efficiently degraded. Strikingly, depletion of endogenous SNX1 by siRNA markedly inhibited agonist-induced PAR1 degradation, whereas expression of a SNX1 siRNA-resistant mutant protein restored agonist-promoted PAR1 degradation in cells lacking endogenous SNX1, indicating that SNX1 is necessary for lysosomal degradation of PAR1. SNX1 is known to interact with components of the mammalian retromer complex and Hrs, an early endosomal membrane-associated protein. However, activated PAR1 degradation was not affected in cells depleted of retromer Vps26/Vps35 subunits, Hrs or Tsg101, an Hrs-interacting protein. We further show that SNX2, which dimerizes with SNX1, is not essential for lysosomal sorting of PAR1, but rather can regulate PAR1 degradation by disrupting endosomal localization of endogenous SNX1 when ectopically expressed. Together, our findings establish an essential role for endogenous SNX1 in sorting activated PAR1 to a distinct lysosomal degradative pathway that is independent of retromer, Hrs, and Tsg101.

Penton base induces better protective immune responses than fiber and hexon as a subunit vaccine candidate against adenoviruses

Vaccine ◽  
2018 ◽  
Vol 36 (29) ◽  
pp. 4287-4297 ◽  
Author(s):  
Kai Hu ◽  
Ming Fu ◽  
Xinmeng Guan ◽  
Di Zhang ◽  
Xu Deng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Penton Base ◽  
A Subunit

scholarly journals The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 974 ◽  
Author(s):  
Shantae M. Thornton ◽  
Varsha D. Samararatne ◽  
Joseph G. Skeate ◽  
Christopher Buser ◽  
Kim P. Lühen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigen Processing ◽  
Viral Antigen ◽  
Essential Role ◽  
Critical Role ◽  
The Body ◽  
Birbeck Granules ◽  
Transmission Electron ◽  
Antigen Presenting

Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.

scholarly journals Cross-linker–mediated regulation of actin network organization controls tissue morphogenesis

2019 ◽  
Vol 218 (8) ◽  
pp. 2743-2761 ◽  
Author(s):  
Daniel Krueger ◽  
Theresa Quinkler ◽  
Simon Arnold Mortensen ◽  
Carsten Sachse ◽  
Stefano De Renzis
Keyword(s):  
Myosin Ii ◽  
Temporal Organization ◽  
Tissue Morphogenesis ◽  
Animal Development ◽  
Spatio Temporal ◽  
Development In Vitro ◽  
Short Time ◽  
Actomyosin Contraction

Contraction of cortical actomyosin networks driven by myosin activation controls cell shape changes and tissue morphogenesis during animal development. In vitro studies suggest that contractility also depends on the geometrical organization of actin filaments. Here we analyze the function of actomyosin network topology in vivo using optogenetic stimulation of myosin-II in Drosophila embryos. We show that early during cellularization, hexagonally arrayed actomyosin fibers are resilient to myosin-II activation. Actomyosin fibers then acquire a ring-like conformation and become contractile and sensitive to myosin-II. This transition is controlled by Bottleneck, a Drosophila unique protein expressed for only a short time during early cellularization, which we show regulates actin bundling. In addition, it requires two opposing actin cross-linkers, Filamin and Fimbrin. Filamin acts synergistically with Bottleneck to facilitate hexagonal patterning, while Fimbrin controls remodeling of the hexagonal network into contractile rings. Thus, actin cross-linking regulates the spatio-temporal organization of actomyosin contraction in vivo, which is critical for tissue morphogenesis.

Evidence for evolutionary conservation of a physical linkage between the human BAF60b, a subunit of SWI/SNF complex, and thyroid hormone receptor interacting protein-1 genes on chromosome 17

Genome ◽  
1999 ◽  
Vol 42 (3) ◽  
pp. 545-549
Author(s):  
Rama Mohan Surabhi ◽  
Lisa Dawn Daly ◽  
Peter A Cattini
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Evolutionary Conservation ◽  
Chromosome 17 ◽  
N Gene ◽  
Interacting Protein ◽  
Physical Linkage ◽  
A Subunit ◽  
Polyadenylation Sites

The ubiquitously expressed rat BAF60b gene, which codes for a subunit of the multiprotein SWI/SNF complex, was recently identified between the pituitary growth hormone (GH-N) and thyroid hormone receptor interacting protein-1 (TRIP-1) genes. In primates, duplication of the GH-N gene has resulted in the addition of four placenta-specific (GH-V, CS-A, CS-B, and CS-L) genes downstream of the GH-N gene. As part of our study of the effect of remote sequences on the transcriptional regulation of the GH/CS gene family, we showed recently that these genes lie 40 kb upstream of the human TRIP-1 gene. We have now investigated the presence of the human BAF60b gene upstream of the TRIP-1 gene for evidence of evolutionary conservation of this arrangement or its disruption by the recent duplication of the nearby GH-N gene in primates. We report that, as in the rat genome, the human BAF60b gene is in the reverse transcriptional direction relative to the TRIP-1 gene, such that their polyadenylation sites are separated by 93 bp which compares with 92 bp in the rat. Reexamination of reported porcine TRIP-1 sequences also revealed the presence of the BAF60b gene separated by 93 bp, supporting an evolutionary conservation of this arrangement.Key words: P1 clone, gene mapping, downstream gene.

An Essential Role for Lipopolysaccharide-Binding Protein in Pulmonary Innate Immune Responses

Shock ◽  
2002 ◽  
Vol 18 (3) ◽  
pp. 248-254 ◽  
Author(s):  
Ming-Hui Fan ◽  
Richard D. Klein ◽  
Lars Steinstraesser ◽  
Andrew C. Merry ◽  
Jean A. Nemzek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Essential Role ◽  
Binding Protein ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Lipopolysaccharide Binding Protein ◽  
Lipopolysaccharide Binding

Involvement of receptor-interacting protein 2 in innate and adaptive immune responses

Nature ◽  
2002 ◽  
Vol 416 (6877) ◽  
pp. 190-194 ◽  
Author(s):  
Arnold I. Chin ◽  
Paul W. Dempsey ◽  
Kevin Bruhn ◽  
Jeff F. Miller ◽  
Yang Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Interacting Protein ◽  
Adaptive Immune
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