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.

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 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 C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent nuclear accumulation of Staufen in neurons

2021 ◽  
Author(s):  
Eun Seon Kim ◽  
Chang Geon Chung ◽  
Jeong Hyang Park ◽  
Byung Su Ko ◽  
Sung Soon Park ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Nuclear Accumulation ◽  
Heterozygous Mutation ◽  
Pathological Feature ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Drosophila Model ◽  
Post Transcriptional Regulation

Abstract RNA-binding proteins (RBPs) play essential roles in diverse cellular processes through post-transcriptional regulation of RNAs. The subcellular localization of RBPs is thus under tight control, the breakdown of which is associated with aberrant cytoplasmic accumulation of nuclear RBPs such as TDP-43 and FUS, well-known pathological markers for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Here, we report in Drosophila model for ALS/FTD that nuclear accumulation of a cytoplasmic RBP, Staufen, may be a new pathological feature. We found that in Drosophila C4da neurons expressing PR36, one of the arginine-rich dipeptide repeat proteins (DPRs), Staufen accumulated in the nucleus in Importin- and RNA-dependent manner. Notably, expressing Staufen with exogenous NLS—but not with mutated endogenous NLS—potentiated PR-induced dendritic defect, suggesting that nuclear-accumulated Staufen can enhance PR toxicity. PR36 expression increased Fibrillarin staining in the nucleolus, which was enhanced by heterozygous mutation of stau (stau+/−), a gene that codes Staufen. Furthermore, knockdown of fib, which codes Fibrillarin, exacerbated retinal degeneration mediated by PR toxicity, suggesting that increased amount of Fibrillarin by stau+/− is protective. Stau+/− also reduced the amount of PR-induced nuclear-accumulated Staufen and mitigated retinal degeneration and rescued viability of flies expressing PR36. Taken together, our data show that nuclear accumulation of Staufen in neurons may be an important pathological feature contributing to the pathogenesis of ALS/FTD.

271 Investigating the Relationship Between Nursery Pig Performance and Markers of Intestinal Morphology and Integrity

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 100-101
Author(s):  
Carson M De Mille ◽  
Nicholas K Gabler
Keyword(s):  
Active Transport ◽  
Feed Intake ◽  
Ex Vivo ◽  
Intestinal Morphology ◽  
Ussing Chambers ◽  
Nursery Pig ◽  
Pig Performance ◽  
Positive Correlations ◽  
And Function ◽  
Time Point

Abstract Weaning induces major structural and function changes to the small intestine of pigs and they transition from milk to solid feedstuffs. Thus, the objective of this study was to determine how intestinal morphology and function markers relate to feed intake and growth rates of nursery pig. Forty-eight weaned pigs (5.63 ± 0.50 kg) were randomly selected, individually penned and fed a common diet. Pig bodyweights and feed intake were determined at d 2, 7, and 21. At each time point, 16 pigs were randomly selected and euthanized. Sections of ileum were assessed for morphology [villus height (VH), crypt depth (CD) and VH:CD] and ex vivo transepithelial resistance (TER), macromolecule permeability (FD4), and active transport of glucose and glutamine via modified Ussing chambers. Within each period (d 0–2, 0–7, and 0–21), Pearson correlations were performed between ADG, ADFI, VH, VH:CD, TER, FD4 and active transport of glucose and glutamine. At d 2 post-weaning, no correlations (P > 0.05) were observed between performance and intestinal variables. By d 7, moderate positive correlations between VH and ADFI (r = 0.69, P = 0.005), VH and ADG (r = 0.68, P = 0.006) were reported. At 21 d post-weaning, moderate positive correlations were still observed for VH and ADFI (r = 0.55, P = 0.026) and between VH and ADG (r = 0.51, P = 0.042). Interestingly, ADFI and ADG tended to be negatively correlated with active glucose transport (r = -0.45, P = 0.083 and r = -0.47, P = 0.064, respectively) and active glutamine transport (r = -0.45, P = 0.083 and r = -0.46, P = 0.073, respectively). Markers of ileal integrity (TER and FD4) were not correlated with ADG or ADFI at any time point. Altogether, these data highlight the importance of intestinal morphology on early nursery pig performance.

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.

scholarly journals Deficiency of the onco-miRNA cluster, miR-106b∼25, causes oligozoospermia and the cooperative action of miR-106b∼25 and miR-17∼92 is required to maintain male fertility

2020 ◽  
Vol 26 (6) ◽  
pp. 389-401
Author(s):  
Alicia Hurtado ◽  
Rogelio Palomino ◽  
Ina Georg ◽  
Miguel Lao ◽  
Francisca M Real ◽  
...  
Keyword(s):  
Male Fertility ◽  
Molecular Mechanisms ◽  
Mirna Cluster ◽  
Knock Out ◽  
Cooperative Action ◽  
Mouse Mutants ◽  
New Genes ◽  
Mirna Clusters ◽  
Testicular Histology ◽  
And Function

Abstract The identification of new genes involved in sexual development and gonadal function as potential candidates causing male infertility is important for both diagnostic and therapeutic purposes. Deficiency of the onco-miRNA cluster miR-17∼92 has been shown to disrupt spermatogenesis, whereas mutations in its paralog cluster, miR-106b∼25, that is expressed in the same cells, were reported to have no effect on testis development and function. The aim of this work is to determine the role of these two miRNA clusters in spermatogenesis and male fertility. For this, we analyzed miR-106b∼25 and miR-17∼92 single and double mouse mutants and compared them to control mice. We found that miR-106b∼25 knock out testes show reduced size, oligozoospermia and altered spermatogenesis. Transcriptomic analysis showed that multiple molecular pathways are deregulated in these mutant testes. Nevertheless, mutant males conserved normal fertility even when early spermatogenesis and other functions were disrupted. In contrast, miR-17∼92+/−; miR-106b∼25−/− double mutants showed severely disrupted testicular histology and significantly reduced fertility. Our results indicate that miR-106b∼25 and miR-17∼92 ensure accurate gene expression levels in the adult testis, keeping them within the required thresholds. They play a crucial role in testis homeostasis and are required to maintain male fertility. Hence, we have identified new candidate genetic factors to be screened in the molecular diagnosis of human males with reproductive disorders. Finally, considering the well-known oncogenic nature of these two clusters and the fact that patients with reduced fertility are more prone to testicular cancer, our results might also help to elucidate the molecular mechanisms linking both pathologies.

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.

scholarly journals Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ranjith K. Papareddy ◽  
Katalin Páldi ◽  
Subramanian Paulraj ◽  
Ping Kao ◽  
Stefan Lutzmayer ◽  
...  
Keyword(s):  
Growth And Development ◽  
Germ Line ◽  
Small Interfering Rnas ◽  
Chromatin States ◽  
Heterochromatin Formation ◽  
Cellular Processes ◽  
A Cell ◽  
Decondensed Chromatin ◽  
And Function ◽  
New Generation

Abstract Background Eukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development and must be properly re-established after its decondensation. Small interfering RNAs (siRNAs) promote heterochromatin formation, but little is known about how chromatin regulates siRNA expression. Results We demonstrate that thousands of transposable elements (TEs) produce exceptionally high levels of siRNAs in Arabidopsis thaliana embryos. TEs generate siRNAs throughout embryogenesis according to two distinct patterns depending on whether they are located in euchromatic or heterochromatic regions of the genome. siRNA precursors are transcribed in embryos, and siRNAs are required to direct the re-establishment of DNA methylation on TEs from which they are derived in the new generation. Decondensed chromatin also permits the production of 24-nt siRNAs from heterochromatic TEs during post-embryogenesis, and siRNA production from bipartite-classified TEs is controlled by their chromatin states. Conclusions Decondensation of heterochromatin in response to developmental, and perhaps environmental, cues promotes the transcription and function of siRNAs in plants. Our results indicate that chromatin-mediated siRNA transcription provides a cell-autonomous homeostatic control mechanism to help reconstitute pre-existing chromatin states during growth and development including those that ensure silencing of TEs in the future germ line.

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