scholarly journals The Modular Adaptive Ribosome

2016 ◽  
Author(s):  
Anupama Yadav ◽  
Aparna Radhakrishnan ◽  
Anshuman Panda ◽  
Amartya Singh ◽  
Himanshu Sinha ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Large Data ◽  
Cell Types ◽  
Ecological Niches ◽  
Environmental Cues ◽  
Dependent Manner ◽  
Yeast Strains ◽  
Specific Manner ◽  
Signatures Of Selection ◽  
Different Cell Types

ABSTRACTThe ribosome is an ancient machine, performing the same function across organisms. Although functionally unitary, recent experiments suggest specialized roles for some ribosomal proteins. Our central thesis is that ribosomal proteins function in a modular fashion to decode genetic information in a context dependent manner. We show through large data analyses that although many ribosomal proteins are essential with consistent effect on growth in different conditions in yeast and similar expression across cell and tissue types in mice and humans, some ribosomal proteins are used in an environment specific manner. The latter set of variable ribosomal proteins further function in a coordinated manner forming modules, which are adapted to different environmental cues in different organisms. We show that these environment specific modules of ribosomal proteins in yeast have differential genetic interactions with other pathways and their 5’UTRs show differential signatures of selection in yeast strains, presumably to facilitate adaptation. Similarly, we show that in higher metazoans such as mice and humans, different modules of ribosomal proteins are expressed in different cell types and tissues. A clear example is nervous tissue that uses a ribosomal protein module distinct from the rest of the tissues in both mice and humans. Our results suggest a novel stratification of ribosomal proteins that could have played a role in adaptation, presumably to optimize translation for adaptation to diverse ecological niches and tissue microenvironments.

scholarly journals The complement of desmosomal plaque proteins in different cell types.

1985 ◽  
Vol 101 (4) ◽  
pp. 1442-1454 ◽  
Author(s):  
P Cowin ◽  
H P Kapprell ◽  
W W Franke
Keyword(s):  
Guinea Pig ◽  
Cell Types ◽  
Cardiac Cells ◽  
Myocardial Tissue ◽  
Cell Type ◽  
Wide Range ◽  
Specific Manner ◽  
A Cell ◽  
Cell Type Specific ◽  
Different Cell Types

Desmosomal plaque proteins have been identified in immunoblotting and immunolocalization experiments on a wide range of cell types from several species, using a panel of monoclonal murine antibodies to desmoplakins I and II and a guinea pig antiserum to desmosomal band 5 protein. Specifically, we have taken advantage of the fact that certain antibodies react with both desmoplakins I and II, whereas others react only with desmoplakin I, indicating that desmoplakin I contains unique regions not present on the closely related desmoplakin II. While some of these antibodies recognize epitopes conserved between chick and man, others display a narrow species specificity. The results show that proteins whose size, charge, and biochemical behavior are very similar to those of desmoplakin I and band 5 protein of cow snout epidermis are present in all desmosomes examined. These include examples of simple and pseudostratified epithelia and myocardial tissue, in addition to those of stratified epithelia. In contrast, in immunoblotting experiments, we have detected desmoplakin II only among cells of stratified and pseudostratified epithelial tissues. This suggests that the desmosomal plaque structure varies in its complement of polypeptides in a cell-type specific manner. We conclude that the obligatory desmosomal plaque proteins, desmoplakin I and band 5 protein, are expressed in a coordinate fashion but independently from other differentiation programs of expression such as those specific for either epithelial or cardiac cells.

Glycogen: a carbohydrate source for GLUT-1 glycosylation during glucose deprivation of 3T3-L1 adipocytes

1996 ◽  
Vol 270 (4) ◽  
pp. E640-E645 ◽  
Author(s):  
R. J. McMahon ◽  
S. C. Frost
Keyword(s):  
Cho Cells ◽  
Chinese Hamster ◽  
Glucose Deprivation ◽  
Cell Types ◽  
Protein Glycosylation ◽  
Dependent Manner ◽  
Glycogen Depletion ◽  
Carbohydrate Source ◽  
Glut 1 ◽  
Different Cell Types

In 3T3-L1 adipocytes, the glycosylation of the GLUT-1 transporter is altered beyond 12 h of glucose deprivation. To determine whether glycogen degradation provides substrate for normal protein glycosylation during this delay, we measured the glycogen content of 3T3-L1 adipocytes. From an initial value of 0.537 +/- 0.097 mumol glucose/10(6) cells, glycogen was depleted in a time-dependent manner in response to glucose deprivation, exhibiting a half-time of 6 h. Surprisingly, fructose did not prevent glycogen depletion. However, in such glycogen-depleted adipocytes, the alteration of GLUT-1 glycosylation in response to glucose deprivation was more rapid than in normal adipocytes. Chinese hamster ovary (CHO) cells, which synthesize abbreviated dolichol-linked oligosaccharides within minutes of glucose deprivation (J. I. Rearick, A. Chapman, and S. Kornfeld. J. Biol. Chem. 256: 6255-6261, 1981), contained only 1% of the level of glycogen found in 3T3-L1 adipocytes. Glycosylation of GLUT-1 was altered in CHO cells within 3 h of glucose deprivation. These data demonstrate that, during glucose stress, glycogen may serve as a buffer for oligosaccharide biosynthesis and provide a potential explanation for varying sensitivities of different cell types to glucose deprivation.

Sensory neurons, neuroimmunity, and pain modulation by sex hormones

Endocrinology ◽  
2021 ◽  
Author(s):  
Melissa E Lenert ◽  
Amanda Avona ◽  
Katherine M Garner ◽  
Luz R Barron ◽  
Michael D Burton
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Cell Types ◽  
Pain Modulation ◽  
National Institutes Of Health ◽  
Neuron Activity ◽  
Sexually Dimorphic ◽  
Dependent Manner ◽  
Biological Variable ◽  
Different Cell Types

Abstract The inclusion of females in preclinical pain studies has become more commonplace in the last decade, as the National Institutes of Health (NIH) “Sex as a Biological Variable” (SABV) mandate was released. Presumably, basic researchers have not had a comprehensive understanding about neuroimmune interactions in half of the population and how hormones play a role in this. To date, we have learned that sex hormones contribute to sexual differentiation of the nervous system and sex differences in behavior throughout the lifespan; however, the cycling of sex hormones does not always explain these differences. Here, we highlight recent advances in our understanding of sex differences and how hormones and immune interactions influence sensory neuron activity to contribute to physiology and pain. Neuroimmune mechanisms may be mediated by different cell types in each sex, as the actions of immune cells are sexually dimorphic. Unfortunately, the majority of studies assessing neuronal contributions to immune function have been limited to males, so it is unclear if the mechanisms are similar in females. Finally, pathways that control cellular metabolism, like nuclear receptors have been shown to play a regulatory role in both pain and inflammation. Overall, communication between the neuroimmune and endocrine systems modulate pain signaling in a sex-dependent manner, but more research is needed to reveal nuances of these mechanisms.

scholarly journals Non-homologous DNA increases gene disruption efficiency by altering DNA repair outcomes

2016 ◽  
Author(s):  
Christopher D Richardson ◽  
Grahm J Ray ◽  
Jacob E Corn
Keyword(s):  
Cell Lines ◽  
Gene Disruption ◽  
Genomic Sequence ◽  
Cell Types ◽  
Polyploid Cell ◽  
Guide Rna ◽  
Homology Directed Repair ◽  
Specific Manner ◽  
A Cell ◽  
Different Cell Types

Cas9 endonuclease can be targeted to genomic sequences by varying the sequence of the single guide RNA (sgRNA). The activity of these Cas9-sgRNA combinations varies widely at different genomic loci and in different cell types. Thus, disrupting genes in polyploid cell lines, or using inefficient sgRNAs, can require extensive downstream screening to identify homozygous clones. We have found that linear, non-homologous oligonucleotide DNA greatly stimulates Cas9-mediated gene disruption in the absence of homology-directed repair. This stimulation greatly increases the frequency of clones with homozygous gene disruptions, even in polyploid cell lines, and rescues otherwise ineffective sgRNAs. The mechanism of enhanced gene disruption differs between human cell lines, stimulating deletion of genomic sequence and/or insertion of non-homologous oligonucleotide DNA at the edited locus in a cell line specific manner. Thus, the addition of non-homologous DNA appears to drive cells towards error-prone instead of error-free repair pathways, dramatically increasing the frequency of gene disruption.

scholarly journals KRAS-related long noncoding RNAs in human cancers

2021 ◽  
Author(s):  
Mahsa Saliani ◽  
Amin Mirzaiebadizi ◽  
Ali Javadmanesh ◽  
Akram Siavoshi ◽  
Mohammad Reza Ahmadian
Keyword(s):  
Mapk Pathway ◽  
Noncoding Rnas ◽  
Cell Types ◽  
Review Article ◽  
Long Noncoding Rnas ◽  
Dependent Manner ◽  
Clinical Tool ◽  
Human Cancers ◽  
Tumor Onset ◽  
Different Cell Types

AbstractKRAS is one of the most widely prevalent proto-oncogenes in human cancers. The constitutively active KRAS oncoprotein contributes to both tumor onset and cancer development by promoting cell proliferation and anchorage-independent growth in a MAPK pathway-dependent manner. The expression of microRNAs (miRNAs) and the KRAS oncogene are known to be dysregulated in various cancers, while long noncoding RNAs (lncRNAs) can act as regulators of the miRNAs targeting KRAS oncogene in different cancers and have gradually become a focus of research in recent years. In this review article, we summarize recent advances in the research on lncRNAs that have sponging effects on KRAS-targeting miRNAs as crucial mediators of KRAS expression in different cell types and organs. A deeper understanding of lncRNA function in KRAS-driven cancers is of major fundamental importance and will provide a valuable clinical tool for the diagnosis, prognosis, and eventual treatment of cancers.

scholarly journals Restricted epithelial proliferation by lacritin via PKCα-dependent NFAT and mTOR pathways

2006 ◽  
Vol 174 (5) ◽  
pp. 689-700 ◽  
Author(s):  
Jiahu Wang ◽  
Ningning Wang ◽  
Jinling Xie ◽  
Staci C. Walton ◽  
Robert L. McKown ◽  
...  
Keyword(s):  
Phospholipase D ◽  
Cell Types ◽  
Secretory Cells ◽  
Dependent Manner ◽  
The Novel ◽  
Receptor Binding Domain ◽  
Epithelial Proliferation ◽  
Α Helix ◽  
Different Cell Types ◽  
Dose Dependent

Renewal of nongermative epithelia is poorly understood. The novel mitogen “lacritin” is apically secreted by several nongermative epithelia. We tested 17 different cell types and discovered that lacritin is preferentially mitogenic or prosecretory for those types that normally contact lacritin during its glandular outward flow. Mitogenesis is dependent on lacritin's C-terminal domain, which can form an α-helix with a hydrophobic face, as per VEGF's and PTHLP's respective dimerization or receptor-binding domain. Lacritin targets downstream NFATC1 and mTOR. The use of inhibitors or siRNA suggests that lacritin mitogenic signaling involves Gαi or Gαo–PKCα-PLC–Ca2+–calcineurin–NFATC1 and Gαi or Gαo–PKCα-PLC–phospholipase D (PLD)–mTOR in a bell-shaped, dose-dependent manner requiring the Ca2+ sensor STIM1, but not TRPC1. This pathway suggests the placement of transiently dephosphorylated and perinuclear Golgi–translocated PKCα upstream of both Ca2+ mobilization and PLD activation in a complex with PLCγ2. Outward flow of lacritin from secretory cells through ducts may generate a proliferative/secretory field as a different unit of cellular renewal in nongermative epithelia where luminal structures predominate.

Induction of cell-specific ribosomal proteins in aggregation-competent nonmorphogenetic Dictyostelium discoideum

1990 ◽  
Vol 68 (11) ◽  
pp. 1281-1287 ◽  
Author(s):  
S. Ramagopal
Keyword(s):  
Ribosomal Proteins ◽  
Cell Types ◽  
Growth Cycle ◽  
Logarithmic Phase ◽  
Cellular Slime Mold ◽  
Developmentally Regulated ◽  
Vegetative Cells ◽  
Competent Cells ◽  
Cellular Slime ◽  
Different Cell Types

Vegetatively growing amoebae, if shaken in a starvation (nonnutrient) buffer, acquire aggregation competence, but do not embark on a morphogenetic program. The quantitative variation of ribosomal proteins in vegetative and aggregation-competent cells was compared by labeling the different cell types with [35S]methionine. Vegetative cells were examined at various phases of the growth cycle. No changes could be detected in the content of ribosomes or the apparent stoichiometry of ribosomal proteins in growing cells. In stationary phase cells, the net ribosome content declined to 15% of that observed in logarithmic phase, but the relative amounts of individual ribosomal proteins were not altered. Although aggregation-competent cells contained 30% less ribosomes compared with logarithmic phase cells, the total fraction of newly made ribosomal proteins was the same in both. In contrast to vegetative cells, distinct changes were induced in the ribosomal proteins of aggregation-competent cells. The composition of ribosomes in aggregation-competent phase resembled in every respect that observed in spore cells. As reported earlier, changes were found in all 12 of the developmentally regulated ribosomal proteins. For the majority of newly made ribosomal proteins during aggregation competence, the stoichiometry was similar to that in logarithmically growing cells. However, the relative synthesis of some was particularly higher (13- to 46-fold for A and L; 3- to 8-fold for D, E, S24, L3, S6, and L4) compared with logarithmic phase cells. About 18 proteins, which included the cell-specific ribosomal proteins L18, S10, S14, S16, and L11, were synthesized in lesser amounts than in logarithmic phase cells. It is concluded that the attainment of aggregation competence is sufficient for the induction of spore cell specific ribosomal proteins in Dictyostelium discoideum.Key words: cellular slime mold, ribosomal proteins, development.

scholarly journals Mechanosensitive calcium signaling in filopodia

2020 ◽  
Author(s):  
Artem K. Efremov ◽  
Mingxi Yao ◽  
Michael P. Sheetz ◽  
Alexander D. Bershadsky ◽  
Boris Martinac ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Crucial Role ◽  
Cell Types ◽  
Molecular Pathways ◽  
Mechanical Forces ◽  
Dependent Manner ◽  
Tensile Forces ◽  
Channel Dependent ◽  
Different Cell Types

AbstractFilopodia are ubiquitous membrane projections that play crucial role in guiding cell migration on rigid substrates and through extracellular matrix by utilizing yet unknown mechanosensing molecular pathways. As recent studies show that Ca2+ channels localized to filopodia play an important role in regulation of their formation and since some Ca2+ channels are known to possess mechanosensing properties, activity of filopodial Ca2+ channels might be tightly interlinked with the filopodia mechanosensing function. We tested this hypothesis by monitoring changes in the intra-filopodial Ca2+ level in response to application of stretching force to individual filopodia of several cell types. It has been found that stretching forces of tens of pN strongly promote Ca2+ influx into filopodia, causing persistent Ca2+ oscillations that last for minutes even after the force is released. Most of the known mechanosensitive Ca2+ channels, such as Piezo 1, Piezo 2 and TRPV4, were found to be dispensable for the observed force-dependent Ca2+ influx. In contrast, L-type Ca2+ channels appear to be a key component in the discovered phenomenon. Since previous studies have shown that intra-filopodial transient Ca2+ signals play an important role in guidance of cell migration, our results suggest that the force-dependent activation of L-type Ca2+ channels may contribute to this process. Overall, our study reveals an intricate interplay between mechanical forces and Ca2+ signaling in filopodia, providing novel mechanistic insights for the force-dependent filopodia functions in guidance of cell migration.Significance statementWe found that tensile forces of tens of pN applied to individual filopodia trigger Ca2+ influx through L-type Ca2+ channels, producing persistent Ca2+ oscillations inside mechanically stretched filopodia. Resulting elevation of the intra-filopodial Ca2+ level in turn leads to downstream activation of calpain protease, which is known to play a crucial role in regulation of the cell adhesion dynamics. Thus, our work suggests that L-type channel-dependent Ca2+ signaling and the mechanosensing function of filopodia are coupled to each other, synergistically governing cell adhesion and motion in a force-dependent manner. Since L-type Ca2+ channels have been previously found in many different cell types, such as neural or cancer cells, the above mechanism is likely to be widespread among various cell lines.

scholarly journals Integrins in point contacts mediate cell spreading: factors that regulate integrin accumulation in point contacts vs. focal contacts.

1993 ◽  
Vol 120 (1) ◽  
pp. 261-271 ◽  
Author(s):  
N Tawil ◽  
P Wilson ◽  
S Carbonetto
Keyword(s):  
Cell Types ◽  
Laminin Receptor ◽  
Dependent Manner ◽  
Point Contacts ◽  
Focal Contacts ◽  
Beta 1 Integrin ◽  
Mediate Cell ◽  
Different Cell Types

We have studied the function and distribution of the alpha 1 beta 1, alpha 5 beta 1 and alpha 6 beta 1 heterodimers on type-1 astrocytes with antibodies specific for integrin subunits (alpha 1, alpha 5, alpha 6, and beta 1). The alpha 1 beta 1 heterodimer mediates adhesion to laminin and collagen, the alpha 5 beta 1 to fibronectin in an RGD-dependent manner. The alpha 5 beta 1 integrin is found in focal contacts in long-term cultures of well-spread astrocytes colocalizing with vinculin and the termini of actin stress fibers. alpha 1 beta 1 heterodimers can occasionally be found as small aggregates within focal contacts but they do not accumulate there. Instead, alpha 1 beta 1 integrins are found in punctate deposits called point contacts which are distributed over the upper and the lower cell surfaces whether laminin, collagen, fibronectin or polylysine is used as a substratum. Unlike focal contacts, point contacts contain clathrin but rarely codistribute with actin or vinculin. Two observations indicate that these point contacts are functional. First, mAb 3A3, directed against the rat alpha 1 subunit, inhibits the attachment of astrocytes to laminin and collagen. Second, during the spreading of astrocytes, a band of point contacts forms around the cell perimeter at a time when no focal contacts are visible. While alpha 1 beta 1 integrins are found only in point contacts in astrocytes, the alpha 6 beta 1 integrin, another laminin receptor, is localized within focal contacts. Moreover, alpha 1 beta 1 heterodimers accumulate in focal contacts in fibroblasts. Thus, the alpha subunit contributes, independent of its ligand, to functional integrin heterodimer accumulation in focal contacts or in point contacts. This accumulation varies among different cell types with apparently identical heterodimers as well as with the motile state (spreading vs. flattened) of the same cells.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 118-119
Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun
Keyword(s):  
Electron Microscopy ◽  
Structural Organization ◽  
Cell Types ◽  
Structural Features ◽  
Molecular Architecture ◽  
The Past ◽  
Keratin Filaments ◽  
Different Types ◽  
10 Nm Filaments ◽  
Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

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