scholarly journals Microtubule motors involved in nuclear movement during skeletal muscle differentiation

2017 ◽  
Vol 28 (7) ◽  
pp. 865-874 ◽  
Author(s):  
V. Gache ◽  
E. R. Gomes ◽  
B. Cadot
Keyword(s):  
Molecular Motors ◽  
Muscle Differentiation ◽  
Nuclear Movement ◽  
Nuclear Positioning ◽  
Cellular Processes ◽  
Nuclear Behavior ◽  
Microtubule Motors ◽  
Microtubule Motor ◽  
Motion Speed ◽  
And Function

Nuclear positioning is a determining event in several cellular processes, such as fertilization, cell migration, and cell differentiation. The structure and function of muscle cells, which contain hundreds of nuclei, have been shown to rely in part on proper nuclear positioning. Remarkably, in the course of muscle differentiation, nuclear movements along the myotube axis might represent the event required for the even positioning of nuclei in the mature myofiber. Here we analyze nuclear behavior, time in motion, speed, and alignment during myotube differentiation and temporal interference of cytoskeletal microtubule-related motors. Using specific inhibitors, we find that nuclear movement and alignment are microtubule dependent, with 19 microtubule motor proteins implicated in at least one nuclear behavior. We further focus on Kif1c, Kif5b, kif9, kif21b, and Kif1a, which affect nuclear alignment. These results emphasize the different roles of molecular motors in particular mechanisms.

scholarly journals Centrosomal and ciliary targeting of CCDC66 requires cooperative action of centriolar satellites, microtubules and molecular motors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Deniz Conkar ◽  
Halil Bayraktar ◽  
Elif Nur Firat-Karalar
Keyword(s):  
Retinal Degeneration ◽  
Gene Product ◽  
Active Transport ◽  
Molecular Motors ◽  
Protein Targeting ◽  
Satellite Dynamics ◽  
Cooperative Action ◽  
Cellular Processes ◽  
Spatiotemporal Regulation ◽  
And Function

Abstract Mammalian centrosomes and cilia play key roles in many cellular processes and their deregulation is linked to cancer and ciliopathies. Spatiotemporal regulation of their biogenesis and function in response to physiological stimuli requires timely protein targeting. This can occur by different pathways, including microtubule-dependent active transport and via centriolar satellites, which are key regulators of cilia assembly and signaling. How satellites mediate their functions and their relationship with other targeting pathways is currently unclear. To address this, we studied retinal degeneration gene product CCDC66, which localizes to centrosomes, cilia, satellites and microtubules and functions in ciliogenesis. FRAP experiments showed that its centrosomal pool was dynamic and the ciliary pool associated with the ciliary axoneme and was stable. Centrosomal CCDC66 abundance and dynamics required microtubule-dependent active transport and tethering, and was inhibited by sequestration at satellites. Systematic quantitation of satellite dynamics identified only a small fraction to display microtubule-based bimodal motility, consistent with trafficking function. Majority displayed diffusive motility with unimodal persistence, supporting sequestration function. Together, our findings reveal new mechanisms of communication between membrane-less compartments.

Dis1/TOG universal microtubule adaptors - one MAP for all?

2001 ◽  
Vol 114 (21) ◽  
pp. 3805-3812 ◽  
Author(s):  
Hiroyuki Ohkura ◽  
Miguel A. Garcia ◽  
Takashi Toda
Keyword(s):  
Molecular Mechanisms ◽  
Binding Activity ◽  
Mitotic Spindles ◽  
Microtubule Associated Proteins ◽  
Cellular Processes ◽  
Microtubule Motors ◽  
Associated Proteins ◽  
On Line ◽  
And Function ◽  
Centrosomal Proteins

Microtubules play central roles in various cellular processes in eukaryotes. The dynamics and organisation of interphase microtubules and mitotic spindles are dramatically altered during the cell cycle and development. However, the molecular mechanisms underlying this dynamic behaviour remain to be understood. In recent years, a novel family of microtubule-associated proteins (MAPs), the Dis1/TOG family, has emerged as a versatile regulator of microtubule function. These MAPs are highly conserved in eukaryotes from yeasts and plants to humans. The localisation and function of these MAPs are not determined simply by their intrinsic microtubule-binding activity. Instead this family executes its diverse roles by interacting with other regulatory molecules, including microtubule motors and centrosomal proteins. The modular structure of these MAPs may allow them to interact with multiple proteins and thereby be involved in a wide variety of microtubule and spindle functions. Movies available on-line

scholarly journals Bidirectional Translocation of Neurofilaments along Microtubules Mediated in Part by Dynein/Dynactin

2000 ◽  
Vol 11 (10) ◽  
pp. 3495-3508 ◽  
Author(s):  
Jagesh V. Shah ◽  
Lisa A. Flanagan ◽  
Paul A. Janmey ◽  
Jean-François Leterrier
Keyword(s):  
Spinal Cord ◽  
Molecular Motors ◽  
Motor Proteins ◽  
Motor Complex ◽  
Microtubule Motors ◽  
Microtubule Motor ◽  
Cytoskeletal Elements

Neuronal cytoskeletal elements such as neurofilaments, F-actin, and microtubules are actively translocated by an as yet unidentified mechanism. This report describes a novel interaction between neurofilaments and microtubule motor proteins that mediates the translocation of neurofilaments along microtubules in vitro. Native neurofilaments purified from spinal cord are transported along microtubules at rates of 100-1000 nm/s to both plus and minus ends. This motion requires ATP and is partially inhibited by vanadate, consistent with the activity of neurofilament-bound molecular motors. Motility is in part mediated by the dynein/dynactin motor complex and several kinesin-like proteins. This reconstituted motile system suggests how slow net movement of cytoskeletal polymers may be achieved by alternating activities of fast microtubule motors.

scholarly journals Escape from mitotic catastrophe by actin-dependent nuclear displacement in fission yeast

2020 ◽  
Author(s):  
Masashi Yukawa ◽  
Yasuhiro Teratani ◽  
Takashi Toda
Keyword(s):  
Cell Division ◽  
Fission Yeast ◽  
Time Lapse ◽  
Mitotic Catastrophe ◽  
Nuclear Movement ◽  
Nuclear Positioning ◽  
Cell Axis ◽  
Cellular Processes ◽  
Daughter Cells ◽  
Actin Cables

SUMMARYProper nuclear positioning is essential for the execution of a wide variety of cellular processes in eukaryotic cells (Gundersen and Worman, 2013; Kopf et al., 2020; Lele et al., 2018). In proliferating mitotic cells, nuclear positioning is crucial for successful cell division. The bipolar spindle, which pulls sister chromatids towards two opposite poles, needs to assemble in the geometrical center of the cell. This ensures symmetrical positioning of the two nuclei that are reformed upon mitotic exit, by which two daughter cells inherit the identical set of the chromosomes upon cytokinesis. In fission yeast, the nucleus is positioned in the cell center during interphase; cytoplasmic microtubules interact with both the nucleus and the cell tips, thereby retaining the nucleus in the medial position of the cell (Daga et al., 2006; Tran et al., 2001). By contrast, how the nucleus is positioned during mitosis remains elusive. Here we show that several cell-cycle mutants that arrest in mitosis all displace the nucleus towards one end of the cell axis. Intriguingly, the actin cytoskeleton, not the microtubule counterpart, is responsible for the asymmetric movement of the nucleus. Time-lapse live imaging indicates that mitosis-specific F-actin cables interact with the nuclear membrane, thereby possibly generating an asymmetrical pushing force. In addition, constriction of the actomyosin ring further promotes nuclear displacement. This nuclear movement is beneficial, because if the nuclei were retained in the cell center, subsequent cell division would impose the lethal cut phenotype (Hirano et al., 1986; Yanagida, 1998), in which chromosomes are intersected by the contractile actin ring and the septum. Thus, fission yeast escapes from mitotic catastrophe by means of actin-dependent nuclear movement.

scholarly journals Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1960
Author(s):  
K. Tanuj Sapra ◽  
Ohad Medalia
Keyword(s):  
Intermediate Filaments ◽  
Eukaryotic Cell ◽  
Coiled Coils ◽  
Cellular Functions ◽  
Mechanical Pressure ◽  
Mechanical Feature ◽  
Cellular Processes ◽  
Nuclear Lamins ◽  
Filament Networks ◽  
And Function

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin.

scholarly journals Ubiquitin and Ubiquitin-Like Proteins and Domains in Ribosome Production and Function: Chance or Necessity?

2021 ◽  
Vol 22 (9) ◽  
pp. 4359
Author(s):  
Sara Martín-Villanueva ◽  
Gabriel Gutiérrez ◽  
Dieter Kressler ◽  
Jesús de la Cruz
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosome Assembly ◽  
Cellular Processes ◽  
Substrate Protein ◽  
Precursor Proteins ◽  
Assembly Factors ◽  
Ubiquitin Moiety ◽  
And Function

Ubiquitin is a small protein that is highly conserved throughout eukaryotes. It operates as a reversible post-translational modifier through a process known as ubiquitination, which involves the addition of one or several ubiquitin moieties to a substrate protein. These modifications mark proteins for proteasome-dependent degradation or alter their localization or activity in a variety of cellular processes. In most eukaryotes, ubiquitin is generated by the proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor, or as a single N-terminal moiety to ribosomal proteins, which are practically invariably eL40 and eS31. Herein, we summarize the contribution of the ubiquitin moiety within precursors of ribosomal proteins to ribosome biogenesis and function and discuss the biological relevance of having maintained the explicit fusion to eL40 and eS31 during evolution. There are other ubiquitin-like proteins, which also work as post-translational modifiers, among them the small ubiquitin-like modifier (SUMO). Both ubiquitin and SUMO are able to modify ribosome assembly factors and ribosomal proteins to regulate ribosome biogenesis and function. Strikingly, ubiquitin-like domains are also found within two ribosome assembly factors; hence, the functional role of these proteins will also be highlighted.

The role of the cytoskeleton in the movement and positioning of nuclei in Coprinus cinereus

1995 ◽  
Vol 73 (S1) ◽  
pp. 364-368 ◽  
Author(s):  
Takashi Kamada ◽  
Shigeru Tanabe
Keyword(s):  
Life Cycle ◽  
Immunofluorescence Microscopy ◽  
Coprinus Cinereus ◽  
Nuclear Movement ◽  
Nuclear Positioning ◽  
Mitotic Apparatus ◽  
Tubulin Mutations ◽  
Early Phases ◽  
Hyphal Apex

Coprinus cinereus exhibits conspicuous nuclear movement and precise nuclear positioning during its life cycle. Examples include transhyphal migration of nuclei in compatible mating giving rise to a dikaryon, nuclear positioning relative to the hyphal apex in the dikaryon, the close spacing in interphase and conjugate division of the two nuclei in the dikaryon, and the migration of nuclei from the basidium into developing spores. We have investigated the roles of the cytoskeleton in these processes using cytoskeleton mutants as well as fluorescence microscopy. Some of the α1- and β1-tubulin mutations examined blocked nuclear migration in dikaryosis and disturbed nuclear pairing in the dikaryon, demonstrating that microtubules are involved in these processes. The same mutations, however, did not affect the positioning of nuclei in interphase nor in conjugate division in the dikaryon, nor the migration of nuclei into the developing spores. Immunofluorescence microscopy revealed that these mutations inhibit the formation of asters of the mitotic apparatus in conjugate division, providing evidence against direct involvement of astral microtubules in nuclear movement during conjugate division. Actin was concentrated in hyphal regions where the nuclei sit in early phases of conjugate division, suggesting the involvement of actin in conjugate division. Key words: Coprinus cinereus, dikaryon, nuclear movement, microtubules, aster, actin.

scholarly journals Akt2 Regulates Cardiac Metabolism and Cardiomyocyte Survival

2006 ◽  
Vol 281 (43) ◽  
pp. 32841-32851 ◽  
Author(s):  
Brian DeBosch ◽  
Nandakumar Sambandam ◽  
Carla Weinheimer ◽  
Michael Courtois ◽  
Anthony J. Muslin
Keyword(s):  
Pressure Overload ◽  
Cardiac Metabolism ◽  
Cellular Protein ◽  
Growth Responses ◽  
Infarct Zone ◽  
Targeted Disruption ◽  
Cellular Processes ◽  
Ligand Stimulation ◽  
And Function

The Akt family of serine-threonine kinases participates in diverse cellular processes, including the promotion of cell survival, glucose metabolism, and cellular protein synthesis. All three known Akt family members, Akt1, Akt2 and Akt3, are expressed in the myocardium, although Akt1 and Akt2 are most abundant. Previous studies demonstrated that Akt1 and Akt3 overexpression results in enhanced myocardial size and function. Yet, little is known about the role of Akt2 in modulating cardiac metabolism, survival, and growth. Here, we utilize murine models with targeted disruption of the akt2 or the akt1 genes to demonstrate that Akt2, but not Akt1, is required for insulin-stimulated 2-[3H]deoxyglucose uptake and metabolism. In contrast, akt2-/- mice displayed normal cardiac growth responses to provocative stimulation, including ligand stimulation of cultured cardiomyocytes, pressure overload by transverse aortic constriction, and myocardial infarction. However, akt2-/- mice were found to be sensitized to cardiomyocyte apoptosis in response to ischemic injury, and apoptosis was significantly increased in the peri-infarct zone of akt2-/- hearts 7 days after occlusion of the left coronary artery. These results implicate Akt2 in the regulation of cardiomyocyte metabolism and survival.

Bioerodible Polypyrrole

2001 ◽  
Vol 711 ◽  
Author(s):  
Alexander Zelikin ◽  
Venkatram Shastri ◽  
David Lynn ◽  
Jian Farhadi ◽  
Ivan Martin ◽  
...  
Keyword(s):  
Erosion Rate ◽  
Acid Group ◽  
The Novel ◽  
Carboxylic Acid Group ◽  
Polymer Backbone ◽  
Cellular Processes ◽  
Novel Approach ◽  
Efficient Control ◽  
And Function ◽  
Substrate Independent

ABSTRACTConductive polymers such as polypyrrole (Ppy) are potentially useful as an active interface for altering cellular processes and function. Their utilization in medically related applications however have been substantially held back by their non-degradable nature. Herein we report a novel approach to creation of bioerodible polypyrroles via modification of pyrrole beta-carbon with an ionizable moiety. It has been shown that the erosion rate of acid-bearing derivative of polypyrrole increases with pH, which is consistent with the pH dependent ionization of carboxylic acid group. The novel paradigm proposed for the creation of bioerodible polypyrroles allows for simple and efficient control over the erosion rate of the substrate independent of the polymer chain length, via the choice of the terminal ionizable group and its concentration along the polymer backbone.

scholarly journals A Potential of microRNAs for High-Content Screening

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Andrius Serva ◽  
Christoph Claas ◽  
Vytaute Starkuviene
Keyword(s):  
Large Scale ◽  
Cellular Processes ◽  
Comprehensive Knowledge ◽  
Functional Models ◽  
Rapid Accumulation ◽  
Health And Disease ◽  
Temporal And Spatial ◽  
And Function ◽  
Functional Analyses ◽  
Immense Potential

In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance of miRNA-based regulation in health and disease has inspired research to investigate diverse aspects of miRNA origin, biogenesis, and function. Despite the recent rapid accumulation of experimental data, and the emergence of functional models, the complexity of miRNA-based regulation is still far from being well understood. In particular, we lack comprehensive knowledge as to which cellular processes are regulated by which miRNAs, and, furthermore, how temporal and spatial interactions of miRNAs to their targets occur. Results from large-scale functional analyses have immense potential to address these questions. In this review, we discuss the latest progress in application of high-content and high-throughput functional analysis for the systematic elucidation of the biological roles of miRNAs.

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