scholarly journals Nanoscale Organization of FasL on DNA Origami as a Versatile Platform to Tune Apoptosis Signaling in Cells

2020 ◽  
Author(s):  
Ricarda M. L. Berger ◽  
Johann M. Weck ◽  
Simon M. Kempe ◽  
Tim Liedl ◽  
Joachim O. Rädler ◽  
...  
Keyword(s):  
Cell Biology ◽  
Fas Ligand ◽  
Dna Origami ◽  
Time To Death ◽  
Naturally Occurring ◽  
Soluble Fasl ◽  
Death Kinetics ◽  
Molecular Number ◽  
Signaling Efficiency ◽  
In Cells

AbstractNanoscale probes with fine-tunable properties are of key interest in cell biology and nanomedicine to elucidate and eventually control signaling processes in cells. A critical, still challenging issue is to conjugate these probes with molecules in a number- and spatially-controlled manner. Here, DNA origami-based nanoagents as nanometer precise scaffolds presenting Fas ligand (FasL) in well-defined arrangements to cells are reported. These nanoagents activate receptor molecules in the plasma membrane initiating apoptosis signaling in cells. Signaling for apoptosis depends sensitively on FasL geometry: fastest time-to-death kinetics are obtained for FasL nanoagents representing predicted structure models of hexagonal receptor ordering with 10 nm inter-molecular spacing. Slower kinetics are observed for one to two FasL on DNA origami or FasL coupled with higher flexibility. Nanoagents with FasL arranged in hexagons with small (5 nm) and large (30 nm) spacing impede signal transduction. Moreover, for predicted hexagonal FasL nanoagents, signaling efficiency is faster and 100× higher compared to naturally occurring soluble FasL. Incubation of the FasL-origami nanoagent in solution exhibited an EC50 value of only 90 pM. These studies present DNA origami as versatile signaling platforms to probe the significance of molecular number and nanoscale ordering for signal initiation in cells.

scholarly journals 3P189 Movement of nucleus in cells cultured on micro-patterned substrates(Cell biology,Poster,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ2014))

2014 ◽  
Vol 54 (supplement1-2) ◽  
pp. S280
Author(s):  
Zhu Xinfeng ◽  
Kuribayashi-Shigetomi Kaori ◽  
Cai Pinggen ◽  
Subagyo Agus ◽  
Sueoka Kazuhisa ◽  
...  
Keyword(s):  
Annual Meeting ◽  
Cell Biology ◽  
Patterned Substrates ◽  
Biophysical Society ◽  
Cells Cultured ◽  
In Cells

scholarly journals Cas3 Protein—A Review of a Multi-Tasking Machine

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 208 ◽  
Author(s):  
Liu He ◽  
Michael St. John James ◽  
Marin Radovcic ◽  
Ivana Ivancic-Bace ◽  
Edward L. Bolt
Keyword(s):  
Cell Biology ◽  
Protein A ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Cellular Processes ◽  
Concise Review ◽  
In Cells

Cas3 has essential functions in CRISPR immunity but its other activities and roles, in vitro and in cells, are less widely known. We offer a concise review of the latest understanding and questions arising from studies of Cas3 mechanism during CRISPR immunity, and highlight recent attempts at using Cas3 for genetic editing. We then spotlight involvement of Cas3 in other aspects of cell biology, for which understanding is lacking—these focus on CRISPR systems as regulators of cellular processes in addition to defense against mobile genetic elements.

Imaging myosin 10 in cells

2004 ◽  
Vol 32 (5) ◽  
pp. 689-693 ◽  
Author(s):  
D. Tacon ◽  
P.J. Knight ◽  
M. Peckham
Keyword(s):  
Green Fluorescent Protein ◽  
Cell Biology ◽  
Fluorescent Protein ◽  
Major Task ◽  
Green Fluorescent ◽  
In Cells

Cellular motors (kinesin, dynein and myosin) are ubiquitous. A major task in cell biology is to determine how they function in cells. Here we focus on myosin 10, an intrafilopodial motor, and show how imaging green fluorescent protein fused to myosin 10 or its tail domains can help us understand the function of this myosin.

scholarly journals An expanded view of the eukaryotic cytoskeleton

2013 ◽  
Vol 24 (11) ◽  
pp. 1615-1618 ◽  
Author(s):  
James B. Moseley
Keyword(s):  
Complex System ◽  
Cell Biology ◽  
Linear Polymers ◽  
Polymer Systems ◽  
History Of ◽  
Definition Of ◽  
Future Work ◽  
Biology Research ◽  
In Cells

A rich and ongoing history of cell biology research has defined the major polymer systems of the eukaryotic cytoskeleton. Recent studies have identified additional proteins that form filamentous structures in cells and can self-assemble into linear polymers when purified. This suggests that the eukaryotic cytoskeleton is an even more complex system than previously considered. In this essay, I examine the case for an expanded definition of the eukaryotic cytoskeleton and present a series of challenges for future work in this area.

scholarly journals Electron Microscopy of the Bovine Cutaneous Papilloma

1966 ◽  
Vol 3 (3) ◽  
pp. 196-207 ◽  
Author(s):  
D. Brobst ◽  
E.J. Hinsman
Keyword(s):  
Electron Microscopy ◽  
Plasma Membranes ◽  
Light And Electron Microscopy ◽  
Degenerative Changes ◽  
Virus Like Particles ◽  
Cytoplasmic Vacuolation ◽  
Naturally Occurring ◽  
Prickle Cell ◽  
In Cells

Experimentally produced bovine cutaneous papillomas of 30, 76 and 112 days' duration as well as 3 naturally occurring bovine cutaneous papillomas were examined by light and electron microscopy. Degenerative changes were not observed in the fibromatous base of the 30-day-old papilloma. An alteration in all papillomas older than 30 days was cytoplasmic vacuolation in cells of the prickle cell and keratohyaline layers. As cells progressed upward their degeneration became more prominent. In the keratinized layers of 2 papillomas virus-like particles were observed within plasma membranes of keratinized cells.

scholarly journals Flice-Inhibitory Protein Expression during Macrophage Differentiation Confers Resistance to FAS-Mediated Apoptosis

1999 ◽  
Vol 190 (11) ◽  
pp. 1679-1688 ◽  
Author(s):  
Harris Perlman ◽  
Lisa J. Pagliari ◽  
Constantinos Georganas ◽  
Toshiaki Mano ◽  
Kenneth Walsh ◽  
...  
Keyword(s):  
Cell Death ◽  
Fas Ligand ◽  
Negative Regulator ◽  
Death Domain ◽  
Blood Monocytes ◽  
Inhibitory Protein ◽  
Monocyte Differentiation ◽  
Host Immune Responses ◽  
Naturally Occurring ◽  
Induced Apoptosis

Macrophages differentiated from circulating peripheral blood monocytes are essential for host immune responses and have been implicated in the pathogenesis of rheumatoid arthritis and atherosclerosis. In contrast to monocytes, macrophages are resistant to Fas-induced cell death by an unknown mechanism. FLICE (Fas-associated death domain–like interleukin 1β–converting enzyme)–inhibitory protein (Flip), a naturally occurring caspase-inhibitory protein that lacks the critical cysteine domain necessary for catalytic activity, is a negative regulator of Fas-induced apoptosis. Here, we show that monocyte differentiation into macrophages was associated with upregulation of Flip and a decrease in Fas-mediated apoptosis. Overexpression of Flip protected monocytes from Fas-mediated apoptosis, whereas acute Flip inhibition in macrophages induced apoptosis. Addition of an antagonistic Fas ligand antibody to Flip antisense–treated macrophages rescued cultures from apoptosis, demonstrating that endogenous Flip blocked Fas-induced cell death. Thus, the expression of Flip in macrophages conferred resistance to Fas-mediated apoptosis, which may contribute to the development of inflammatory disease.

scholarly journals Naturally Occurring Human Immunodeficiency Virus Type 1 Long Terminal Repeats Have a Frequently Observed Duplication That Binds RBF-2 and Represses Transcription

1998 ◽  
Vol 72 (8) ◽  
pp. 6465-6474 ◽  
Author(s):  
Mario Clemente Estable ◽  
Brendan Bell ◽  
Martin Hirst ◽  
Ivan Sadowski
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Binding Sites ◽  
Naturally Occurring ◽  
Immunodeficiency Virus ◽  
Aids Study ◽  
Hiv 1 ◽  
In Cells

ABSTRACT Approximately 38% of human immunodeficiency virus type 1 (HIV-1)-infected patients within the Vancouver Lymphadenopathy-AIDS Study have proviruses bearing partial 15- to 34-nucleotide duplications upstream of the NF-κB binding sites within the 5′ long terminal repeat (LTR). This most frequent naturally occurring length polymorphism (MFNLP) of the HIV-1 5′ LTR encompasses potential binding sites for several candidate transcription factors, including TCF-1α/hLEF, c-Ets, AP-4, and Ras-responsive binding factor 2 (RBF-2) (M. C. Estable et al., J. Virol. 70:4053–4062, 1996). RBF-2 and an apparently related factor, RBF-1, bind to at least fourcis elements within the LTR which are required for full transcriptional responsiveness to protein-tyrosine kinases and v-Ras (B. Bell and I. Sadowski, Oncogene 13:2687–2697, 1996). Here we demonstrate that representative MFNLPs from two patients specifically bind RBF-2. In both cases, deletion of the MFNLP caused elevated LTR-directed transcription in cells expressing RBF-2 but not in cells with undetectable RBF-2. RBF-1, but not RBF-2, appears to contain the Ets transcription factor family member GABPα/GABPβ1. Taken together with the fact that every MFNLP from a comparative study of over 500 LTR sequences from 42 patients contains a predicted binding site for RBF-2, our data suggest that the MFNLP is selected in vivo because it provides a duplicated RBF-2 cis element, which may limit transcription in monocytes and activated T cells.

scholarly journals Spatial heterogeneity of the cytosol revealed by machine learning-based 3D particle tracking

2020 ◽  
Vol 31 (14) ◽  
pp. 1498-1511 ◽  
Author(s):  
Grace A. McLaughlin ◽  
Erin M. Langdon ◽  
John M. Crutchley ◽  
Liam J. Holt ◽  
M. Gregory Forest ◽  
...  
Keyword(s):  
Machine Learning ◽  
Spatial Heterogeneity ◽  
Particle Tracking ◽  
Cell Biology ◽  
Physical State ◽  
Biological Systems ◽  
Physical Structure ◽  
Length Scales ◽  
3D Motion ◽  
In Cells

The structure of the cytosol across different length scales is a debated topic in cell biology. Here we present tools to measure the physical state of the cytosol by analyzing the 3D motion of nanoparticles expressed in cells. We find evidence that the physical structure of the cytosol is a fundamental source of variability in biological systems.

scholarly journals 1P191 Actin dynamics in cells cultured on engineered micro-topographical substrate(12.Cell biology,Poster,The 51st Annual Meeting of the Biophysical Society of Japan)

2013 ◽  
Vol 53 (supplement1-2) ◽  
pp. S137
Author(s):  
Hiromi Miyoshi ◽  
Takuma Kishimoto ◽  
Takehiko Inaba ◽  
Miki Nishimura ◽  
Michiko Sugawara ◽  
...  
Keyword(s):  
Annual Meeting ◽  
Cell Biology ◽  
Actin Dynamics ◽  
Biophysical Society ◽  
Cells Cultured ◽  
In Cells

Fas ligand is targeted to secretory lysosomes via a proline-rich domain in its cytoplasmic tail

2001 ◽  
Vol 114 (13) ◽  
pp. 2405-2416 ◽  
Author(s):  
Emma J. Blott ◽  
Giovanna Bossi ◽  
Richard Clark ◽  
Marketa Zvelebil ◽  
Gillian M. Griffiths
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Fas Ligand ◽  
Cytoplasmic Tail ◽  
Cell Types ◽  
Cell Surface Receptor ◽  
Cell Surface Expression ◽  
Rich Domain ◽  
Secretory Lysosomes ◽  
In Cells

Fas ligand (FasL) induces apoptosis through its cell surface receptor Fas. T lymphocytes and natural killer cells sort newly synthesised FasL to secretory lysosomes but, in cell types with conventional lysosomes, FasL appears directly on the plasma membrane. Here, we define a proline-rich domain (PRD) in the cytoplasmic tail of FasL that is responsible for sorting FasL to secretory lysosomes. Deletion of this PRD results in cell surface expression of FasL in cells with secretory lysosomes. Positively charged residues flanking the PRD are crucial to the sorting motif and changing the charge of these residues causes mis-sorting to the plasma membrane. In cells with conventional lysosomes, this motif is not recognised and FasL is expressed at the plasma membrane. The FasL PRD is not required for endocytosis in any cell type, as deletion mutants lacking this motif are endocytosed efficiently to the lysosomal compartment. Endogenous FasL cannot internalise extracellular antibody, demonstrating that FasL does not transit the plasma membrane en route to the secretory lysosomes. We propose that an interaction of the PRD of FasL with an SH3-domain-containing protein, enables direct sorting of FasL from the Golgi to secretory lysosomes.

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