Intracellular Cytoskeletal Elements and Cytoskeletons in Bacteria

Within a short period of time after the discovery of bacterial cytoskletons, major progress had been made in areas such as general spatial layout of cytoskeletons, their involvement in a variety of cell functions (shape control, cell division, chromosome segregation, cell motility). This progress was achieved by application of advanced investigation techniques. Homologs of eukaryotic actin, tubulin, and intermediate filaments were found in bacteria; cytoskeletal proteins not closely or not at all related to any of these major cytoskeletal proteins were discovered in a number of bacteria such as Mycoplasmas, Spiroplasmas, Spirochetes, Treponema, Caulobacter. A structural role for bacterial elongation factor Tu was indicated. On the basis of this new thinking, new approaches in biotechnology and new drugs are on the way.

Download Full-text

Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

Molecules ◽

10.3390/molecules26133866 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3866

Author(s):

Natasha Irrera ◽

Alessandra Bitto ◽

Emanuela Sant’Antonio ◽

Rita Lauro ◽

Caterina Musolino ◽

...

Keyword(s):

Cannabinoid Receptors ◽

Hematological Malignancies ◽

Antitumor Agents ◽

Control Cell ◽

Experimental Studies ◽

Endocannabinoid System ◽

Chemotherapeutic Agents ◽

Cancer Cell Growth ◽

Cell Functions ◽

Novel Approach

The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable. Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma. Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance. Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.

Download Full-text

Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol.

Molecular Biology of the Cell ◽

10.1091/mbc.8.3.533 ◽

1997 ◽

Vol 8 (3) ◽

pp. 533-545 ◽

Cited By ~ 159

Author(s):

T Harder ◽

R Kellner ◽

R G Parton ◽

J Gruenberg

Keyword(s):

Actin Cytoskeleton ◽

Cytoskeletal Proteins ◽

Annexin Ii ◽

Dependent Manner ◽

Cortical Actin ◽

Independent Manner ◽

Low Concentrations ◽

Early Endosomes ◽

Associated Proteins ◽

Cytoskeletal Elements

Annexin II is an abundant protein which is present in the cytosol and on the cytoplasmic face of plasma membrane and early endosomes. It is generally believed that this association occurs via Ca(2+)-dependent binding to lipids, a mechanism typical for the annexin protein family. Although previous studies have shown that annexin II is involved in early endosome dynamics and organization, the precise biological role of the protein is unknown. In this study, we found that approximately 50% of the total cellular annexin was associated with membranes in a Ca(2+)-independent manner. This binding was extremely tight, since it resisted high salt and, to some extent, high pH treatments. We found, however, that membrane-associated annexin II could be quantitatively released by low concentrations of the cholesterol-sequestering agents filipin and digitonin. Both treatments released an identical and limited set of proteins but had no effects on other membrane-associated proteins. Among the released proteins, we identified, in addition to annexin II itself, the cortical cytoskeletal proteins alpha-actinin, ezrin and moesin, and membrane-associated actin. Our biochemical and immunological observations indicate that these proteins are part of a complex containing annexin II and that stability of the complex is sensitive to cholesterol sequestering agents. Since annexin II is tightly membrane-associated in a cholesterol-dependent manner, and since it seems to interact physically with elements of the cortical actin cytoskeleton, we propose that the protein serves as interface between membranes containing high amounts of cholesterol and the actin cytoskeleton.

Download Full-text

Cytoskeletal proteins associate with components of the ribosomal maturation and translation apparatus in Xenopus stage I oocytes

Zygote ◽

10.1017/s0967199414000409 ◽

2014 ◽

Vol 23 (5) ◽

pp. 669-682 ◽

Cited By ~ 5

Author(s):

Loredana Chierchia ◽

Margherita Tussellino ◽

Domenico Guarino ◽

Rosa Carotenuto ◽

Nadia DeMarco ◽

...

Keyword(s):

Protein Synthesis ◽

Elongation Factor ◽

Cytoskeletal Proteins ◽

Stage I ◽

Initiation Factor ◽

Perinuclear Region ◽

Eukaryotic Initiation Factor ◽

Translation Apparatus ◽

Ribosomal Stalk

SummaryActin-based cytoskeleton (CSK) and microtubules may bind to RNAs and related molecules implicated in translation. However, many questions remain to be answered regarding the role of cytoskeletal components in supporting the proteins involved in steps in the maturation and translation processes. Here, we performed co-immunoprecipitation and immunofluorescence to examine the association between spectrins, keratins and tubulin and proteins involved in 60S ribosomal maturation and translation in Xenopus stage I oocytes, including ribosomal rpl10, eukaryotic initiation factor 6 (Eif6), thesaurins A/B, homologs of the eEF1α elongation factor, and P0, the ribosomal stalk protein. We found that rpl10 and eif6 cross-reacted with the actin-based CSK and with tubulin. rpl10 co-localizes with spectrin, particularly in the perinuclear region. eif6 is similarly localized. Given that upon ribosomal maturation, the insertion of rpl10 into the 60S subunit occurs simultaneously with the release of eif6, one can hypothesise that actin-based CSK and microtubules provide the necessary scaffold for the insertion/release of these two molecules and, subsequently, for eif6 transport and binding to the mature 60S subunit. P0 and thesaurins cross-reacted with only spectrin and cytokeratins. Thesaurins aggregated at the oocyte periphery, rendering this a territory favourable site for protein synthesis; the CSK may support the interaction between thesaurins and sites of the translating ribosome. Moreover, given that the assembly of the ribosome stalk, where P0 is located, to the 60S subunit is essential for the release of eif6, it can be hypothesised that the CSK can facilitate the binding of the stalk to the 60S.

Download Full-text

Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro.

Acta Biochimica Polonica ◽

10.18388/abp.2000_4068 ◽

2000 ◽

Vol 47 (1) ◽

pp. 113-120 ◽

Cited By ~ 3

Author(s):

K Bielawski ◽

A Galicka ◽

A Bielawska ◽

K Sredzińska

Keyword(s):

Protein Biosynthesis ◽

Elongation Factor ◽

Inhibitory Effect ◽

New Drugs ◽

Clinical Use ◽

Inhibitory Effects ◽

Inhibit Protein Synthesis ◽

Primary Target ◽

Eukaryotic Elongation Factor

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system. The three compounds differed in the precise mode of action. The inhibitory effect of I on the activity of the eukaryotic elongation factor eEF-2 and ribosomes seems to suggest that the binding site of eEF-2 on the ribosome was blocked by this compound. eEF-2 has been identified as the primary target of II and eEF-1 as the primary target of DAPI in the system studied.

Download Full-text

Archaeal cell biology: diverse functions of tubulin-like cytoskeletal proteins at the cell envelope

Emerging Topics in Life Sciences ◽

10.1042/etls20180026 ◽

2018 ◽

Vol 2 (4) ◽

pp. 547-559 ◽

Cited By ~ 2

Author(s):

Yan Liao ◽

Solenne Ithurbide ◽

Roshali T. de Silva ◽

Susanne Erdmann ◽

Iain G. Duggin

Keyword(s):

Cell Biology ◽

Shape Control ◽

Cell Envelope ◽

Light And Electron Microscopy ◽

Halophilic Archaea ◽

Cytoskeletal Proteins ◽

Model Organisms ◽

Full Spectrum ◽

Peptidoglycan Cell Wall ◽

Domains Of Life

The tubulin superfamily of cytoskeletal proteins is widespread in all three domains of life — Archaea, Bacteria and Eukarya. Tubulins build the microtubules of the eukaryotic cytoskeleton, whereas members of the homologous FtsZ family construct the division ring in prokaryotes and some eukaryotic organelles. Their functions are relatively poorly understood in archaea, yet these microbes contain a remarkable diversity of tubulin superfamily proteins, including FtsZ for division, a newly described major family called CetZ that is involved in archaeal cell shape control, and several other divergent families of unclear function that are implicated in a variety of cell envelope-remodelling contexts. Archaeal model organisms, particularly halophilic archaea such as Haloferax volcanii, have sufficiently developed genetic tools and we show why their large, flattened cells that are capable of controlled differentiation are also well suited to cell biological investigations by live-cell high-resolution light and electron microscopy. As most archaea only have a glycoprotein lattice S-layer, rather than a peptidoglycan cell wall like bacteria, the activity of the tubulin-like cytoskeletal proteins at the cell envelope is expected to vary significantly, and may involve direct membrane remodelling or directed synthesis or insertion of the S-layer protein subunits. Further studies of archaeal cell biology will provide fresh insight into the evolution of cells and the principles in common to their fundamental activities across the full spectrum of cellular life.

Download Full-text

Partitioning of symbiotic Chlorella at host cell telophase in the green hydra symbiosis

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1990.0148 ◽

1990 ◽

Vol 329 (1252) ◽

pp. 47-53 ◽

Cited By ~ 6

Keyword(s):

Cell Division ◽

Host Cell ◽

Daughter Cell ◽

Control Cell ◽

Culture Conditions ◽

Digestive Cells ◽

Density Dependent ◽

Green Hydra ◽

The Mean ◽

Control Cell Division

Although there is much evidence that green hydra digestive cells control cell division of their Chlorella symbionts, so that the symbionts divide only at host cell division, it is not clear how the population size of symbionts (numbers per cell) is regulated. In constant culture conditions the mean number of symbionts per cell also remains constant, but with a very large variance about the mean. The way in which symbionts are partitioned at host cell division appears to account for that variation. By counting numbers of Chlorella in daughter cells at late telophase it was found that partitioning of Chlorella symbionts was not symmetrical, but at random, closely following that predicted by the binomial distribution if it is assumed that each symbiont had an equal probability of entering either host daughter cell. A better fit to the predicted distribution was obtained from observations of partition in digestive cells from excised regenerating peduncles than in those from recently fed gastric regions, possibly because in the former, algae have completed their division before the host cell divides, while in the latter algal and host cell division takes place at the same time. There was only a small effect of differences in daughter cell volume on numbers of symbionts received, but comparison of variance and coefficient of variation of numbers of algae in mother (post-algal division, pre-partition) and daughter telophase digestive cells (pre-division, post-partition) suggested that algal division at host mitosis was density dependent. Random partitioning of algae at host cell telophase would account for the wide variation in numbers of algae per cell, and compensatory density-dependent algal division at the next host cell mitosis would ensure stability of the mean algal population.

Download Full-text

Reversal of Growth Suppression by p107 via Direct Phosphorylation by Cyclin D1/Cyclin-Dependent Kinase 4

Molecular and Cellular Biology ◽

10.1128/mcb.22.7.2242-2254.2002 ◽

2002 ◽

Vol 22 (7) ◽

pp. 2242-2254 ◽

Cited By ~ 49

Author(s):

Xiaohong Leng ◽

Martin Noble ◽

Peter D. Adams ◽

Jun Qin ◽

J. Wade Harper

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Control Cell ◽

Growth Suppression ◽

Cyclin Dependent Kinase ◽

Culture Cells ◽

Cycle Arrest ◽

A Cell ◽

Control Cell Division

ABSTRACT p107 functions to control cell division and development through interaction with members of the E2F family of transcription factors. p107 is phosphorylated in a cell cycle-regulated manner, and its phosphorylation leads to its release from E2F. Although it is known that p107 physically associates with E- and A-type cyclin/cyclin-dependent kinase 2 (Cdk2) complexes through a cyclin-binding RXL motif located in the spacer domain, the mechanisms underlying p107 inactivation via phosphorylation remain poorly defined. Recent genetic evidence indicates a requirement for cyclin D1/Cdk4 complexes in p107 inactivation. In this work, we provide direct biochemical evidence for the involvement of cyclin D1/Cdk4 in the inactivation of p107's growth-suppressive function. While coexpression of cyclin D1/Cdk4 can reverse the cell cycle arrest properties of p107 in Saos-2 cells, we find that p107 in which the Lys-Arg-Arg-Leu sequence of the RXL motif is replaced by four alanine residues is largely refractory to inactivation by cyclin D/Cdk4, indicating a role for this motif in p107 inactivation without a requirement for its tight interaction with cyclin D1/Cdk4. We identified four phosphorylation sites in p107 (Thr-369, Ser-640, Ser-964, and Ser-975) that are efficiently phosphorylated by Cdk4 but not by Cdk2 in vitro and are also phosphorylated in tissue culture cells. Growth suppression by p107 containing nonphosphorylatable residues in these four sites is not reversed by coexpression of cyclin D1/Cdk4. In model p107 spacer region peptides, phosphorylation of S640 by cyclin D1/Cdk4 is strictly dependent upon an intact RXL motif, but phosphorylation of this site in the absence of an RXL motif can be partially restored by replacement of S643 by arginine. This suggests that one role for the RXL motif is to facilitate phosphorylation of nonconsensus Cdk substrates. Taken together, these data indicate that p107 is inactivated by cyclin D1/Cdk4 via direct phosphorylation and that the RXL motif of p107 plays a role in its inactivation by Cdk4 in the absence of stable binding.

Download Full-text