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Derek Bryant, Lara Clemens, Jun Allard
Many actin structures are nucleated and assembled by the barbed-end tracking polymerase formin family, including filopodia, focal adhesions, the cytokinetic ring and cell cortex. These structures respond to forces in distinct ways. Formins typically have profilin-actin binding sites embedded in highly flexible disordered FH1 domains, hypothesized to diffusively explore space to rapidly capture actin monomers for delivery to the barbed end. Recent experiments demonstrate that formin mediated polymerization accelerates when under tension...
October 28, 2016: Cytoskeleton
Philip R Nicovich, Miro Janco, Tom Sobey, Mehul Gajwani, Peyman Obeidy, Renee Whan, Katharina Gaus, Peter Gunning, Adelle Cf Coster, Till Böcking
Reconstitution of actin filaments on surfaces for observation of filament-associated protein dynamics by fluorescence microscopy is currently an exciting field in biophysics. Here we examine the effects of attaching actin filaments to surfaces on the binding and dissociation kinetics of a fluorescence-labelled tropomyosin, a rod-shaped protein that forms continuous strands wrapping around the actin filament. Two attachment modalities of the actin to the surface are explored: where the actin filament is attached to the surface at multiple points along its length; and where the actin filament is attached at one end and aligned parallel to the surface by buffer flow...
October 26, 2016: Cytoskeleton
Anna Hegsted, Forrest A Wright, SarahBeth Votra, David Pruyne
Formins are regulators of actin filament dynamics. We demonstrate here that two formins, FHOD-1 and EXC-6, are important in the nematode Caenorhabditis elegans for ovulation, during which actomyosin contractions push a maturing oocyte from the gonad arm into a distensible bag-like organ, the spermatheca. EXC-6, a homolog of the disease-associated mammalian formin INF2, is highly expressed in the spermatheca, where it localizes to cell-cell junctions and to circumferential actin filament bundles. Loss of EXC-6 does not noticeably affect the organization the actin filament bundles, and causes only a very modest increase in the population of junction-associated actin filaments...
October 22, 2016: Cytoskeleton
Katsutoshi Mizuno, Erin E Dymek, Elizabeth F Smith
The complex waveforms characteristic of motile eukaryotic cilia and flagella are produced by the temporally and spatially regulated action of multiple dynein subforms generating sliding between subsets of axonemal microtubules. Multiple protein complexes have been identified that are associated with the doublet microtubules and that mediate regulatory signals between key axonemal structures, such as the radial spokes and central apparatus, and the dynein arm motors; these complexes include the N-DRC, MIA and CSC complexes...
October 22, 2016: Cytoskeleton
Amalia R Driller-Colangelo, Karen W L Chau, Jessica M Morgan, Nathan D Derr
Cytoplasmic dynein is a minus-end directed microtubule-based motor protein that drives intracellular cargo transport in eukaryotic cells. Although many intracellular cargos are propelled by small groups of dynein motors, the biophysical mechanisms governing ensemble motility remain largely unknown. To investigate the emergent motility of motor ensembles, we have designed a programmable DNA origami synthetic cargo "chassis" enabling us to control the number of dynein motors in the ensemble and vary the rigidity of the cargo chassis itself...
October 8, 2016: Cytoskeleton
Charles B Lindemann, Kathleen A Lesich
The eukaryotic flagellum is the organelle responsible for the propulsion of the male gamete in most animals. Without exception, sperm of all mammalian species use a flagellum for swimming. The mammalian sperm has a centrally located 9 + 2 arrangement of microtubule doublets and hundreds of accessory proteins that together constitute an axoneme. However, they also possess several characteristic peri-axonemal structures that make the mammalian sperm tail function differently. These modifications include nine outer dense fibers (ODFs) that are paired with the nine outer microtubule doublets of the axoneme, and are anchored in a structure called the connecting piece located at the base...
November 2016: Cytoskeleton
Shailaja Seetharaman, Ella Flemyng, Jiazhen Shen, Maria R Conte, Anne J Ridley
LARP4 is a La-related RNA-binding protein implicated in regulating mRNA translation, which interacts with poly(A)-binding protein (PABP). We previously identified LARP4 in an RNAi screen as one of several genes that regulate the shape of PC3 prostate cancer cells. Here we show that LARP4 depletion induces cell elongation in PC3 cells and MDA-MB-231 breast cancer cells. LARP4 depletion increases cell migration and invasion, as well as inducing invasive cell protrusions in 3D Matrigel. Conversely, LARP4 over-expression reduces cell elongation and increases cell circularity...
November 2016: Cytoskeleton
Farooq Ahmad Kiani, Stefan Fischer
The ATPase active site of myosin is located at the core of the motor head. During the Lymn-Taylor actomyosin contractile cycle, small conformational changes in the active site upon ATP binding, ATP hydrolysis and ADP/Pi release are accompanied by large conformational transitions of the motor domains, such as opening and closing of the actin binding cleft and the movement of lever arm. Here, our previous computational studies of myosin are summarized in a comprehensive model at the level of atomic detail. Molecular movies show how the successive domain motions during the ATP induced actin dissociation and the recovery stroke are coupled with the precise positioning of the key catalytic groups in the active site...
November 2016: Cytoskeleton
Nathan E Grega-Larson, Scott W Crawley, Matthew J Tyska
Cordon-bleu (COBL) is a multifunctional WASP-Homology 2 (WH2) domain-containing protein implicated in a wide variety of cellular functions ranging from dendritic arborization in neurons to the assembly of microvilli on the surface of transporting epithelial cells. In vitro biochemical studies suggest that COBL is capable of nucleating and severing actin filaments, among other activities. How the multiple activities of COBL observed in vitro contribute to its function in cells remains unclear. Here, we used live imaging to evaluate the impact of COBL expression on the actin cytoskeleton in cultured cells...
November 2016: Cytoskeleton
Rodrigo López-Leal, Jaime Alvarez, Felipe A Court
The structural homeostasis is challenging for neurons, whose axons extend up to meters in large animals, and the axoplasmic mass reaches over a thousand times that of the cell body. Thus, the protein demand may overcome the capacity of the cell body to supply the right protein species, to the right place, in the right time. In this context, a body of evidence indicates that glial cells support the axonal maintenance and regenerative responses by diverse mechanisms of intercellular communication. We showed recently that Schwann cells (SC) transfer ribosomes to axons and also enhance regeneration by means of extracellular vesicles known as exosomes that contain mRNAs, miRNAs and proteins...
October 2016: Cytoskeleton
Carlos Wilson, Jonathan R Terman, Christian González-Billault, Giasuddin Ahmed
Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through noncovalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function...
October 2016: Cytoskeleton
David Villarroel-Campos, Francisca C Bronfman, Christian Gonzalez-Billault
Neurons are highly polarized cells that contain specialized subcellular domains involved in information transmission in the nervous system. Specifically, the somatodendritic compartment receives neuronal inputs while the axons convey information through the synapse. The establishment of asymmetric domains requires a specific delivery of components, including organelles, proteins, and membrane. The Rab family of small GTPases plays an essential role in membrane trafficking. Signaling cascades triggered by extrinsic and intrinsic factors tightly regulate Rab functions in cells, with Rab protein activation depending on GDP/GTP binding to establish a binary mode of action...
September 2016: Cytoskeleton
Peter W Baas, Anand N Rao, Andrew J Matamoros, Lanfranco Leo
Neurons are terminally differentiated cells that use their microtubule arrays not for cell division but rather as architectural elements required for the elaboration of elongated axons and dendrites. In addition to acting as compression-bearing struts that provide for the shape of the neuron, microtubules also act as directional railways for organelle transport. The stability properties of neuronal microtubules are commonly discussed in the biomedical literature as crucial to the development and maintenance of the nervous system, and have recently gained attention as central to the etiology of neurodegenerative diseases...
September 2016: Cytoskeleton
James R Bamburg, Barbara W Bernstein
Cytoskeletal abnormalities and synaptic loss, typical of both familial and sporadic Alzheimer disease (AD), are induced by diverse stresses such as neuroinflammation, oxidative stress, and energetic stress, each of which may be initiated or enhanced by proinflammatory cytokines or amyloid-β (Aβ) peptides. Extracellular Aβ-containing plaques and intracellular phospho-tau-containing neurofibrillary tangles are postmortem pathologies required to confirm AD and have been the focus of most studies. However, AD brain, but not normal brain, also have increased levels of cytoplasmic rod-shaped bundles of filaments composed of ADF/cofilin-actin in a 1:1 complex (rods)...
September 2016: Cytoskeleton
Iryna Hlushchenko, Mikko Koskinen, Pirta Hotulainen
The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines. The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines. Synaptic activity patterns rapidly change actin dynamics, leading to morphological changes in dendritic spines. In this mini-review, we will discuss recent findings on neuronal maturation and synaptic plasticity-induced changes in the dendritic spine actin cytoskeleton...
September 2016: Cytoskeleton
Shanxi Feng, Don B Arnold
This review focused on techniques that facilitated the visualization of protein trafficking. In the mid-1990s the cloning of GFP allowed fluorescently tagged proteins to be expressed in cells and then visualized in real time. This advance allowed a glimpse, for the first time, of the complex system within cells for distributing proteins. It quickly became apparent, however, that time-lapse sequences of exogenously expressed GFP-labeled proteins can be difficult to interpret. Reasons for this include the relatively low signal that comes from moving proteins and high background rates from stationary proteins and other sources, as well as the difficulty of identifying the origins and destinations of specific vesicular carriers...
September 2016: Cytoskeleton
Sérgio Carvalho Leite, Mónica Mendes Sousa
The role of the actin cytoskeleton in neurons has been extensively studied in actin-enriched compartments such as the growth cone and dendritic spines. The recent discovery of actin rings in the axon shaft and in dendrites, together with the identification of axon actin trails, has advanced our understanding on actin organization and dynamics in neurons. However, specifically in the case of actin rings, the mechanisms regulating their nucleation and assembly, and the functions that they may exert in axons and dendrites remain largely unexplored...
September 2016: Cytoskeleton
Garrett M Cammarata, Elizabeth A Bearce, Laura Anne Lowery
The growth cone is a unique structure capable of guiding axons to their proper destinations. Within the growth cone, extracellular guidance cues are interpreted and then transduced into physical changes in the actin filament (F-actin) and microtubule cytoskeletons, providing direction and movement. While both cytoskeletal networks individually possess important growth cone-specific functions, recent data over the past several years point towards a more cooperative role between the two systems. Facilitating this interaction between F-actin and microtubules, microtubule plus-end tracking proteins (+TIPs) have been shown to link the two cytoskeletons together...
September 2016: Cytoskeleton
Valeria Panzetta, Marta De Menna, Ida Musella, Mariagabriella Pugliese, Maria Quarto, Paolo A Netti, Sabato Fusco
Alterations in the cytoskeleton structure are frequently found in several diseases and particularly in cancer cells. It is also through the alterations of the cytoskeleton structure that cancer cells acquire most of their common features such as uncontrolled cell proliferation, cell death evasion and the gaining of migratory and invasive characteristics. Although radiation therapies currently represent one of the most effective treatments for patients, the effects of X-irradiation on the cytoskeleton architecture are still poorly understood...
August 17, 2016: Cytoskeleton
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