scholarly journals The conserved metalloprotease invadolysin is present in invertebrate haemolymph and vertebrate blood

2019 ◽  
Author(s):  
Kanishk Abhinav ◽  
Linda Feng ◽  
Emma Morrison ◽  
Yunshin Jung ◽  
James Dear ◽  
...  
Keyword(s):  
Extracellular Vesicle ◽  
Sexually Dimorphic ◽  
Post Translational Modifications ◽  
Glycogen Accumulation ◽  
Extracellular Milieu ◽  
Metabolic Role ◽  
Storage Organelle ◽  
Summary Statement ◽  
And Migration ◽  
Accumulation Of Lipids

AbstractWe identified invadolysin, a novel essential metalloprotease, for functions in chromosome structure, cell proliferation and migration. Invadolysin also plays an important metabolic role in insulin signaling and is the only protease known to localise to lipid droplets, the main lipid storage organelle in the cell. In silico examination of the protein sequence of invadolysin predicts not only protease and lipase catalytic motifs, but also post-translational modifications and the secretion of invadolysin. Here we show that the protease motif of invadolysin is important for its role in lipid accumulation, but not in glycogen accumulation. The lipase motif does not appear to be functionally important for accumulation of lipids or glycogen. Post-translational modifications likely contribute to modulating the level, localisation or activity of invadolysin. We identified a secreted form of invadolysin in the soluble fraction of invertebrate hemolymph (where we observe sexually dimorphic forms) and also vertebrate plasma, including in the extracellular vesicle fraction. Biochemical analysis for various post-translational modifications demonstrated that secreted invadolysin is both N-and O-glycosylated, but not apparently GPI-linked. The discovery of invadolysin in the extracellular milieu suggests a role for invadolysin in normal organismal physiology.Summary StatementIn this study, we show that the conserved metalloprotease invadolysin is present in invertebrate hemolymph and vertebrate blood, suggesting the protein may function in organismal physiology.

scholarly journals Extracellular-Vesicle-Based Coatings Enhance Bioactivity of Titanium Implants—SurfEV

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Titanium Surface ◽  
Wound Closure ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Tissue Growth ◽  
Titanium Implants ◽  
The Body ◽  
High Concentrations ◽  
And Migration

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.

scholarly journals Arming the troops: Post-translational modification of extracellular bacterial proteins

2020 ◽  
Vol 103 (4) ◽  
pp. 003685042096431
Author(s):  
Suzanne Forrest ◽  
Martin Welch
Keyword(s):  
Cell Surface ◽  
Protein Secretion ◽  
Potential Functions ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Extracellular Milieu ◽  
Bacterial Proteins

Protein secretion is almost universally employed by bacteria. Some proteins are retained on the cell surface, whereas others are released into the extracellular milieu, often playing a key role in virulence. In this review, we discuss the diverse types and potential functions of post-translational modifications (PTMs) occurring to extracellular bacterial proteins.

scholarly journals Probing the mechanisms of extracellular vesicle biogenesis and function in cancer

2018 ◽  
Vol 46 (5) ◽  
pp. 1137-1146 ◽  
Author(s):  
Arash Latifkar ◽  
Richard A. Cerione ◽  
Marc A. Antonyak
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Extracellular Vesicle ◽  
Rna Transcripts ◽  
Main Class ◽  
Vesicle Biogenesis ◽  
And Migration ◽  
And Function ◽  
Cell Phenotypes

Tumor cells interact with each other, and their surroundings, using a variety of mechanisms to promote virtually all aspects of cancer progression. One such form of intercellular communication that has been attracting considerable attention from the cancer community and the pharmaceutical industry in recent years involves the ability of cancer cells to generate multiple distinct types of non-classical secretory vesicles, generally referred to as extracellular vesicles (EVs). Microvesicles (MVs) represent one of the major classes of EVs and are formed as a result of the outward budding and fission of the plasma membrane. The other main class of EVs is exosomes, which are generated when multivesicular bodies fuse with the cell surface and release their contents into the extracellular space. Both MVs and exosomes have been shown to contain bioactive cargo, including proteins, metabolites, RNA transcripts, microRNAs, and DNA that can be transferred to other cancer cells and stimulate their growth, survival, and migration. However, cancer cell-derived EVs also play important roles in helping re-shape the tumor microenvironment to support tumor expansion and invasive activity, dampen immune responses, as well as enter the circulation to help promote metastatic spread. Here, we provide an overview of what is currently known regarding how the different classes of EVs are generated and contribute to various cancer cell phenotypes. Moreover, we highlight how some of the unique properties of EVs are being used for the development of novel diagnostic and clinical applications.

scholarly journals Microtubule glycylation promotes basal body attachment to the cell cortex

2019 ◽  
Author(s):  
Anthony D. Junker ◽  
Adam W. J. Soh ◽  
Eileen T. O’Toole ◽  
Janet B. Meehl ◽  
Mayukh Guha ◽  
...  
Keyword(s):  
Light Microscopy ◽  
Tetrahymena Thermophila ◽  
Hydrodynamic Flow ◽  
Cell Cortex ◽  
Basal Bodies ◽  
Post Translational Modifications ◽  
Summary Statement ◽  
Motile Cilia ◽  
Em Tomography ◽  
Cortical Cytoskeleton

ABSTRACTMotile cilia generate directed hydrodynamic flow that is important for the motility of cells and extracellular fluids. To optimize directed hydrodynamic flow, motile cilia are organized and oriented into a polarized array. Basal bodies (BB) nucleate and position motile cilia at the cell cortex. Cytoplasmic BB-associated microtubules are conserved structures that extend from BBs. Using the ciliate, Tetrahymena thermophila, combined with EM-tomography and light microscopy, we show that BB-appendage microtubules assemble coincident with new BB assembly and are attached to the cell cortex. These BB-appendage microtubules are specifically marked with post translational modifications of tubulin, including glycylation. Mutations that prevent glycylation shorten BB-appendage microtubules and disrupt BB positioning and cortical attachment. Consistent with the attachment of BB-appendage microtubules to the cell cortex for BB positioning, mutations that disrupt the cellular cortical cytoskeleton similarly disrupt the cortical attachment and positioning of BBs. In summary, BB-appendage microtubules promote the organization of ciliary arrays through attachment to the cell cortex.SUMMARY STATEMENTBasal bodies position motile cilia at the cell cortex. This study finds tubulin glycylation to promote BB-associated microtubule elongation and structural attachment of basal bodies to the cell’s cortical cytoskeleton.

Effect of IL-15-Mediating IFN-γ on HTR-8/SVneo Cells and a Preeclampsia Mouse Model Induced by Lipopolysaccharides

2021 ◽  
pp. 1-10
Author(s):  
Xiao-Lu Wang
Keyword(s):  
Mouse Model ◽  
Morphological Changes ◽  
Kidney Injury ◽  
Annexin V ◽  
Urine Protein ◽  
Junctional Zone ◽  
Glycogen Accumulation ◽  
Invasion And Migration ◽  
Ifn Γ ◽  
And Migration

<b><i>Objective:</i></b> Determine the effect of interleukin (IL)-15 on HTR-8/SVneo cells and a preeclampsia (PE) mouse model induced by LPS. <b><i>Methods:</i></b> Transwell and Annexin-V-FITC/PI assays were performed in HTR-8/SVneo cells transfected with IL-15 activation plasmid/siRNA prior to LPS treatment. Additionally, pregnant mice were injected with LPS and IL-15 siRNA followed by measurement of systolic blood pressure (SBP), urine protein, and serum NO. HE staining was used to observe the morphological changes of the placenta and kidney. Glycogen accumulation was detected using Best’s carmine. qRT-PCR, Western blotting, and ELISA were performed to detect mRNA and protein expression. <b><i>Results:</i></b> LPS increased IL-15 and IFN-γ expression in HTR-8/SVneo cells, and IL-15 positively regulated IFN-γ expression in LPS-induced HTR-8/SVneo cells. Moreover, LPS promoted apoptosis and reduced the invasion and migration of HTR-8/SVneo cells, which was, further, promoted by IL-15 overexpression but attenuated by IL-15 inhibition. Furthermore, LPS increased SBP and urine protein but decreased serum NO in mice, and these factors were reversed by IL-15 siRNA. Downregulation of IL-15 also mitigated kidney injury and improved pregnancy outcomes in LPS-induced PE mice. A significantly thicker junctional zone (JZ) and thinner labyrinth layer were found in placentas of PE mice treated with IL-15 siRNA, along with increased glycogen trophoblast cells in the JZ. Moreover, decreased IFN-γ and <i>NKp46</i> were found in placentas of PE mice treated with IL-15 siRNA. <b><i>Conclusion:</i></b> IL-15 inhibition reduced cell apoptosis and increased the invasive and migratory abilities of LPS-induced HTR-8/SVneo cells, thereby alleviating the PE-like phenotype and improving pregnancy outcome.

scholarly journals PFKFB4 control of Akt signaling is essential for premigratory and migratory neural crest formation

2017 ◽  
Author(s):  
Ana Leonor Figueiredo ◽  
Frédérique Maczkowiak ◽  
Caroline Borday ◽  
Patrick Pla ◽  
Meghane Sittewelle ◽  
...  
Keyword(s):  
Neural Crest ◽  
Early Phase ◽  
Akt Signaling ◽  
Neural Plate ◽  
Summary Statement ◽  
And Migration ◽  
Craniofacial Defects ◽  
Later Phase ◽  
Adult Cells

Summary statementPFKFB4 controls neural crest final specification and migration by regulation of AKT signaling or glycolysis.AbstractNeural crest (NC) specification comprises an early phase, initiating immature NC progenitors formation at neural plate stage, and a later phase at neural fold stage, resulting into functional premigratory NC, able to delaminate and migrate. We found that the NC-GRN triggers up-regulation of pfkfb4 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4) during this late specification phase. As shown in previous studies, PFKFB4 controls AKT signaling in gastrulas and glycolysis rate in adult cells. Here, we focus on PFKFB4 function in NC during and after neurulation, using time-controlled or hypomorph depletions in vivo. We find that PFKFB4 is essential both for specification of functional premigratory NC and for its migration. PFKFB4-depleted embryos fail activating n-cadherin and late NC specifiers, exhibit severe migration defects, resulting in craniofacial defects. AKT signaling mediates PFKFB4 function in NC late specification, while both AKT signaling and glycolysis regulate migration. These findings highlight novel and critical roles of PFKFB4 activity in later stages of NC development, wired into the NC-GRN.

scholarly journals Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development

2021 ◽  
Author(s):  
Seiya Yamada ◽  
Ayaka Sato ◽  
Hiroki Akiyama ◽  
Shin-ichi Sakakibara
Keyword(s):  
Brain Development ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitochondrial Morphology ◽  
Peptidase Activity ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Specific Protease ◽  
And Migration

ABSTRACTBrain development is a highly orchestrated process requiring spatiotemporally regulated mitochondrial dynamics. Drp1, a key molecule in the mitochondrial fission machinery, undergoes various post-translational modifications including conjugation to the small ubiquitin-like modifier (SUMO). However, the functional significance of SUMOylation/deSUMOylation on Drp1 remains controversial. SUMO-specific protease 5 (Senp5L) catalyzes the deSUMOylation of Drp1. We revealed that a splicing variant of Senp5L, Senp5S, which lacks peptidase activity, prevents deSUMOylation of Drp1 by competing against other Senps. The altered SUMOylation level of Drp1 induced by Senp5L/5S affects Drp1 ubiquitination and tubulation of the endoplasmic reticulum (ER), thereby influencing mitochondrial morphology. A dynamic SUMOylation/deSUMOylation balance controls neuronal polarization and migration during the development of the cerebral cortex. These findings suggest a novel role of post translational modification, in which a deSUMOylation enzyme isoform competitively regulates mitochondrial dynamics and ER tubulation via Drp1 SUMOylation levels in a tightly controlled process of neuronal differentiation and corticogenesis.

scholarly journals Dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity

2017 ◽  
Author(s):  
Astrid Veβ ◽  
Ulrich Blache ◽  
Laura Leitner ◽  
Angela R.M. Kurz ◽  
Anja Ehrenpfordt ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Focal Adhesion ◽  
Three Dimensional ◽  
Suspension Cells ◽  
Adhesion Protein ◽  
Cell Matrix ◽  
Mutual Regulation ◽  
Summary Statement ◽  
And Migration ◽  
Focal Adhesion Protein

AbstractPlasticity between adhesive and less-adhesive states is important for mammalian cell behaviour. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of MDA-MB-468 breast carcinoma cells which grows in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced on mRNA and protein level in suspension cells. Furthermore, challenging breast cancer cells transiently with non-adherent conditions markedly reduces Tns3 expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental cells results in defective adhesion, spreading and migration. Tns3 knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a critical focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells.Summary statementWe identify the cell-matrix adapter protein tensin3 as a determinant of adhesion plasticity, using cancer cells selected for non-adherent growth. Tensin3 expression constitutes a feedback loop controlling adhesion and motility.

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