scholarly journals The membrane-actin linker ezrin acts as a sliding anchor

2021 ◽  
Author(s):  
Elgin Korkmazhan ◽  
Alexander Robert Dunn
Keyword(s):  
Cell Membrane ◽  
Actin Cytoskeleton ◽  
Cell Motility ◽  
Single Molecule ◽  
Molecular Mechanisms ◽  
Optical Trap ◽  
Trap Assay ◽  
Rapid Changes

Protein linkages to filamentous (F)-actin provide the cell membrane with mechanical resiliency and give rise to intricate membrane architectures. However, the actin cytoskeleton is highly dynamic, and undergoes rapid changes in shape during cell motility and other processes. The molecular mechanisms that underlie the mechanically robust yet fluid connection between the membrane and actin cytoskeleton remain poorly understood. Here, we used a single-molecule optical trap assay to examine how the prototypical membrane-actin linker ezrin acts to anchor F-actin to the cell membrane. Remarkably, we find that ezrin forms a complex that slides along F-actin over micron distances while resisting mechanical detachment. The ubiquity of ezrin and analogous proteins suggests that sliding anchors such as ezrin may constitute an important but overlooked element in the construction of the actin cytoskeleton.

Cell motility: can Rho GTPases and microtubules point the way?

2001 ◽  
Vol 114 (21) ◽  
pp. 3795-3803 ◽  
Author(s):  
Torsten Wittmann ◽  
Clare M. Waterman-Storer
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Motility ◽  
Rho Gtpases ◽  
Molecular Mechanisms ◽  
Rho Gtpase ◽  
Cell Types ◽  
Small Gtpases ◽  
Cell Polarization ◽  
Microtubule Cytoskeleton ◽  
Filament Bundles

Migrating cells display a characteristic polarization of the actin cytoskeleton. Actin filaments polymerise in the protruding front of the cell whereas actin filament bundles contract in the cell body, which results in retraction of the cell’s rear. The dynamic organization of the actin cytoskeleton provides the force for cell motility and is regulated by small GTPases of the Rho family, in particular Rac1, RhoA and Cdc42. Although the microtubule cytoskeleton is also polarized in a migrating cell, and microtubules are essential for the directed migration of many cell types, their role in cell motility is not well understood at a molecular level. Here, we discuss the potential molecular mechanisms for interplay of microtubules, actin and Rho GTPase signalling in cell polarization and motility. Recent evidence suggests that microtubules locally modulate the activity of Rho GTPases and, conversely, Rho GTPases might be responsible for the initial polarization of the microtubule cytoskeleton. Thus, microtubules might be part of a positive feedback mechanism that maintains the stable polarization of a directionally migrating cell.

scholarly journals Switch-like control of helicase processivity by single-stranded DNA binding protein

2020 ◽  
Author(s):  
Barbara Stekas ◽  
Masayoshi Honda ◽  
Maria Spies ◽  
Yann R. Chemla
Keyword(s):  
Dna Binding ◽  
Single Molecule ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Optical Trap ◽  
Dna Binding Protein ◽  
Single Stranded Dna ◽  
Associated Proteins ◽  
Underlying Mechanisms ◽  
Xpd Helicase

Helicases utilize the energy of NTP hydrolysis to translocate along single-stranded nucleic acids (NA) and unwind the duplex. In the cell, helicases function in the context of other NA-associated proteins which regulate helicase function. For example, single-stranded DNA binding proteins are known to enhance helicase activity, although the underlying mechanisms remain largely unknown. F. acidarmanus XPD helicase serves as a model for understanding the molecular mechanisms of Superfamily 2B helicases, and previous work has shown that its activity is enhanced by the cognate single-stranded DNA binding protein RPA2. Here, single-molecule optical trap measurements of the unwinding activity of a single XPD helicase in the presence of RPA2 reveal a mechanism in which XPD interconverts between two states with different processivities and transient RPA2 interactions stabilize the more processive state, activating a latent “processivity switch” in XPD. These findings provide new insights on mechanisms of helicase regulation by accessory proteins.

scholarly journals Correlative nanophotonic approaches to enlighten the nanoscale dynamics of living cell membranes

2021 ◽  
Author(s):  
Pamina M. Winkler ◽  
María F. García-Parajo
Keyword(s):  
Extracellular Matrix ◽  
Cell Membrane ◽  
Actin Cytoskeleton ◽  
Single Molecule ◽  
Living Cell ◽  
Cell Membranes ◽  
Cell Function ◽  
Membrane Dynamics ◽  
Correlation Spectroscopy ◽  
Spatiotemporal Resolution

Dynamic compartmentalization is a prevailing principle regulating the spatiotemporal organization of the living cell membrane from the nano- up to the mesoscale. This non-arbitrary organization is intricately linked to cell function. On living cell membranes, dynamic domains or ‘membrane rafts' enriched with cholesterol, sphingolipids and other certain proteins exist at the nanoscale serving as signaling and sorting platforms. Moreover, it has been postulated that other local organizers of the cell membrane such as intrinsic protein interactions, the extracellular matrix and/or the actin cytoskeleton synergize with rafts to provide spatiotemporal hierarchy to the membrane. Elucidating the intricate coupling of multiple spatial and temporal scales requires the application of correlative techniques, with a particular need for simultaneous nanometer spatial precision and microsecond temporal resolution. Here, we review novel fluorescence-based techniques that readily allow to decode nanoscale membrane dynamics with unprecedented spatiotemporal resolution and single-molecule sensitivity. We particularly focus on correlative approaches from the field of nanophotonics. Notably, we introduce a versatile planar nanoantenna platform combined with fluorescence correlation spectroscopy to study spatiotemporal heterogeneities on living cell membranes at the nano- up to the mesoscale. Finally, we outline remaining future technological challenges and comment on potential directions to advance our understanding of cell membrane dynamics under the influence of the actin cytoskeleton and extracellular matrix in uttermost detail.

scholarly journals Hopping and Flipping of RNA Polymerase on DNA during Recycling for Reinitiation after Intrinsic Termination in Bacterial Transcription

2021 ◽  
Vol 22 (5) ◽  
pp. 2398
Author(s):  
Wooyoung Kang ◽  
Seungha Hwang ◽  
Jin Young Kang ◽  
Changwon Kang ◽  
Sungchul Hohng
Keyword(s):  
Single Molecule ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Facilitated Diffusion ◽  
One Dimensional ◽  
Bacterial Transcription ◽  
Fluorescence Measurements ◽  
Dimensional Diffusion ◽  
Single Molecule Studies ◽  
Hopping Diffusion

Two different molecular mechanisms, sliding and hopping, are employed by DNA-binding proteins for their one-dimensional facilitated diffusion on nonspecific DNA regions until reaching their specific target sequences. While it has been controversial whether RNA polymerases (RNAPs) use one-dimensional diffusion in targeting their promoters for transcription initiation, two recent single-molecule studies discovered that post-terminational RNAPs use one-dimensional diffusion for their reinitiation on the same DNA molecules. Escherichia coli RNAP, after synthesizing and releasing product RNA at intrinsic termination, mostly remains bound on DNA and diffuses in both forward and backward directions for recycling, which facilitates reinitiation on nearby promoters. However, it has remained unsolved which mechanism of one-dimensional diffusion is employed by recycling RNAP between termination and reinitiation. Single-molecule fluorescence measurements in this study reveal that post-terminational RNAPs undergo hopping diffusion during recycling on DNA, as their one-dimensional diffusion coefficients increase with rising salt concentrations. We additionally find that reinitiation can occur on promoters positioned in sense and antisense orientations with comparable efficiencies, so reinitiation efficiency depends primarily on distance rather than direction of recycling diffusion. This additional finding confirms that orientation change or flipping of RNAP with respect to DNA efficiently occurs as expected from hopping diffusion.

scholarly journals Infrared nanospectroscopy reveals the molecular interaction fingerprint of an aggregation inhibitor with single Aβ42 oligomers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Francesco Simone Ruggeri ◽  
Johnny Habchi ◽  
Sean Chia ◽  
Robert I. Horne ◽  
Michele Vendruscolo ◽  
...  
Keyword(s):  
Small Molecules ◽  
Single Molecule ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Chemical Sensitivity ◽  
Incomplete Knowledge ◽  
Parkinson’S Diseases ◽  
Aggregation Inhibitor ◽  
Misfolding Diseases

AbstractSignificant efforts have been devoted in the last twenty years to developing compounds that can interfere with the aggregation pathways of proteins related to misfolding disorders, including Alzheimer’s and Parkinson’s diseases. However, no disease-modifying drug has become available for clinical use to date for these conditions. One of the main reasons for this failure is the incomplete knowledge of the molecular mechanisms underlying the process by which small molecules interact with protein aggregates and interfere with their aggregation pathways. Here, we leverage the single molecule morphological and chemical sensitivity of infrared nanospectroscopy to provide the first direct measurement of the structure and interaction between single Aβ42 oligomeric and fibrillar species and an aggregation inhibitor, bexarotene, which is able to prevent Aβ42 aggregation in vitro and reverses its neurotoxicity in cell and animal models of Alzheimer’s disease. Our results demonstrate that the carboxyl group of this compound interacts with Aβ42 aggregates through a single hydrogen bond. These results establish infrared nanospectroscopy as a powerful tool in structure-based drug discovery for protein misfolding diseases.

A DNA Molecular Robot Autonomously Walking on the Cell Membrane to Drive the Cell Motility

2021 ◽  
Author(s):  
Hao Li ◽  
Jing Gao ◽  
Lei Cao ◽  
Xuan Xie ◽  
Jiahui Fan ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Motility

A DNA Molecular Robot Autonomously Walking on the Cell Membrane to Drive the Cell Motility

2021 ◽  
Author(s):  
Hao Li ◽  
Jing Gao ◽  
Lei Cao ◽  
Xuan Xie ◽  
Jiahui Fan ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Cell Motility

Dynamic control of cell-cell adhesion and membrane-associated actin during food-induced mouth opening in Beroe

1993 ◽  
Vol 106 (1) ◽  
pp. 355-364
Author(s):  
S.L. Tamm ◽  
S. Tamm
Keyword(s):  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Dynamic Control ◽  
Mouth Opening ◽  
Cell Junctions ◽  
Dynamic Changes ◽  
Rhodamine Phalloidin ◽  
Rapid Changes ◽  
Muscular Action

We used rhodamine-phalloidin and ultrastructural methods to follow dynamic changes in adhesive cell junctions and associated actin filaments during reversible epithelial adhesion in the mouth of the ctenophore Beroe. A cruising Beroe keeps its mouth closed by interdigitated actin-coated appositions between paired strips of cells lining the lips. The mouth opens rapidly (in 0.2-0.3 s) by muscular action to engulf prey (other ctenophores), then re-seals after ingestion. We found that the interlocking surface architecture of the adhesive cells, including the actin-coated junctions, rapidly disappears after food-induced opening of the mouth. In contrast, forcible separation of the lips in the absence of food rips the junctions, still intact, from the surfaces of the cells. The prey-stimulated loss of adhesive cell junctions and associated actin cytoskeleton is one of the most rapid changes in actin-based junctions yet observed. This system provides unique experimental advantages for investigating the dynamic control of reversible cell adhesions and membrane-associated actin filaments.

scholarly journals Research progress on the antibacterial mechanisms of carvacrol: a mini review

2018 ◽  
Vol 1 (6) ◽  
pp. 71
Author(s):  
Dan Zhang ◽  
Ren-You Gan ◽  
Ying-Ying Ge ◽  
Qiong-Qiong Yang ◽  
Jiao Ge ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Antibacterial Activity ◽  
Quorum Sensing ◽  
Cell Membrane ◽  
Molecular Mechanisms ◽  
Food Preservation ◽  
Research Progress ◽  
Oxygen Species ◽  
Aromatic Plants ◽  
Volatile Oils

Background: Carvacrol is an aromatic phenolic terpenoid widely existing in the volatile oils of thyme, oregano, and some other aromatic plants. Recent studies have found that carvacrol possesses excellent antibacterial activity. In order to provide an updated information about the antibacterial potentials of carvacrol, herein, we summarized recent publications about the antibacterial activity of carvacrol, with special attention paid to its antibacterial molecular mechanisms, including desrupting cell membrane, depleting intracellular ATP, inducing reactive oxygen species, inhibiting efflux pumps, as well as suppressing two important virulence factors, biofilm and quorum sensing. In conclusion, carvacrol is a promising natural antibacterial compound with potential application in food preservation and infection.Keywords：Carvacrol, antibacterial mechanisms, biofilm, quorum sensing

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