The role of cell membrane in the regulation of cell division and malignant transformation

An earlier model in which uptake of essential nutrients for which the cell is auxotrophic, regulates cell division, is discussed in the light of new experimental findings, specifically the purification of a new type of transport-inhibitory protein from rat liver and the properties of the protein. The possible role of such proteins in malignant transformation is also discussed.     

Induction of efficient cell division in alfalfa protoplasts

Alfalfa (Medicago sativa L.) protoplasts derived from cell suspension cultures divided inefficiently in liquid culture. The onset of cell division activity occurred synchronously among the protoplasts; however, many were blocked at cytokinesis and therefore did not complete first division. Very few of the cells that began to divide continued to do so. Immobilization of protoplasts in agarose after 1 to 4 days in liquid culture overcame this inhibition of division. Continuous growth in agarose was restricted and therefore microcolonies were transferred to agar medium to complete callus development. Plating efficiencies of 2–10% were achieved within 30 days of protoplast isolation. The agarose treatment was responsible for a 5- to 30-fold improvement in plating efficiency.Contribution No. 774 Ottawa Research Station     

Stem cell self-renewal: The role of asymmetric division

Asymmetric division occurs widely in different groups of organisms from single-celled to insects, mammals, and plants. The operation of asymmetrical division may differ widely in different organisms. In multicellular organisms, asymmetrical division is one of the essential features of stem cell biology. The data obtained assume one of the main biological functions of asymmetrical division to be maintenance of cell viability, beginning with stem cells. Cells continuously accumulate toxic inclusions, which are formed by damaged proteins which cannot be degraded by proteasomes. As a result of asymmetric division, these inclusions segregate into one of the daughter cells providing the ability of long-lived proliferation to another cell.     

Induction of unspecific permeabilization of mitochondrial membrane and its role in cell death

Mitochondria participate in various vital cellular processes. Violation of their functions can lead to the development of cardiovascular and neurodegenerative diseases and malignancies. One of the key events responsible for mitochondrial damage—induction of Ca²⁺-dependent mitochondrial permeability transition, due to the opening of a nonspecific pore in the inner mitochondrial membrane. Despite active studies of pore components, its detailed structure has not yet been established. This review analyzes possible constituents and regulators of the pore, the role of the pore in various pathologies, and hypotheses that explain the organization of the pores. Elucidation of these questions can help developing strategies for the treatment of a wide range of pathologies—from Alzheimer and Parkinson’s disease to cancer.     

Nucleoid-independent identification of cell division sites in Escherichia coli

The mechanism used by Escherichia coli to determine the correct site for cell division is unknown. In this report, we have attempted to distinguish between a model in which septal position is determined by the position of the nucleoids and a model in which septal position is predetermined by a mechanism that does not involve nucleoid position. To do this, filaments with extended nucleoid-free regions adjacent to the cell poles were produced by simultaneous inactivation of cell division and DNA replication. The positions of septa that formed within the nucleoid-free zones after division was allowed to resume were then analyzed. The results showed that septa were formed at a uniform distance from cell poles when division was restored, with no relation to the distance from the nearest nucleoid. In some cells, septa were formed directly over nucleoids. These results are inconsistent with models that invoke nucleoid positioning as the mechanism for determining the site of division site formation.     

The regulatory role of silicon in cell division

Several reports have suggested that silicon has an activating effect on cell proliferation. In order to test this hypothesis, both peripheral human lymphocytes and LDV/7 lymphoblast cells were cultured in the presence of a compound composed of monomethylsilanetriol (silanol), a soluble organic form of silicon, and serine. This molecule stimulates peripheral lymphocyte proliferation at an optimal concentration of 10 mg of silicon per liter of culture medium; in identical conditions, it inhibits the growth of lymphoblasto?d cells (p less than 0.001). Silanol-serine also inhibits the growth of PHA stimulated lymphocytes. The effect of silicon on cell growth has a negative correlation (p less than 0.001) with the mitotic activity of cultured cells: the more intense the latter, the stronger is the inhibitory effect of silanol-serine. This would suggest a regulatory role of this compound on the cell cycle.     

Mitochondrial fusion and division: Regulation and role in cell viability

Discovery of various molecular components regulating dynamics and organization of the mitochondria in cells, together with novel insights into the role of mitochondrial fusion and division in the maintenance of cellular homeostasis, have provided some of the most exciting breakthroughs in the last decade of mitochondrial research. The focus of this review is on the regulation of mitochondrial fusion and division machineries. The newly identified factors associated with mitofusin/OPA1-dependent mitochondrial fusion, and Drp1-dependent mitochondrial division are discussed. Furthermore, the most recent findings on the role of mitochondrial fusion and division in the maintenance of cell function are also reviewed here in some detail.     

Cationic lipid enhances assembly of bacterial cell division protein FtsZ: a possible role of bacterial membrane in FtsZ assembly dynamics

The assembly of FtsZ plays an important role in bacterial cell division. Lipids in the bacterial cell membrane have been suggested to play a role in directing the site of FtsZ assembly. Using lipid monolayer and bilayer (liposome) systems, we directly examined the effects of cationic lipids on FtsZ assembly. We found that cationic lipids enhanced the assembly of FtsZ in association with an increase in the GTPase activity of FtsZ. The system consisting of lipid monolayer and bilayer (liposome) may mimic the bacterial membrane and therefore, the data might indicate the influence of bacterial membrane on the assembly of FtsZ protofilaments.     

The surface membrane as a regulator of animal cell division

Summary The surface membrane of an animal cell is proposed to be the target for regulation of cell division. It undergoes regular periodic changes during the cell division cycle. Interference with these changes by cell-cell surface contacts is proposed to prevent the normal progression of events, and thereby can change the metabolic pattern so as to put the cells into a resting state. Through external influences, cells can escape from this resting state; when this occurs surface changes are the earliest ones observed. Cells that have become malignant, particularly after virus infection, show marked changes in their surface properties. Infection is proposed to prevent the surface changes that lead to the resting state. Recent evidence from in vitro experiments is summarized, and some speculations are made on the connection between the surface and processes of division such as nuclear replication. Presented in the Symposium on Regulation in Tumor Cells at the 22nd Annual Meeting of the Tissue Culture Association. Lake Placid, New York. This work was supported by Public Health Service Grant CA-A1-1195 and Grant E-555 from the American Cancer Society.     

The role of cAMP in controlling yeast cell division

The studies on the cAMP-requiring mutants and their suppressors in the yeast, Saccharomyces cerevisiae, revealed that cAMP-dependent protein phosphorylation is involved in the G1 phase of the cell cycle, in conjugation, and in the post-meiotic stage of sporulation, and that inhibition of cAMP-dependent protein phosphorylation is required to induce meiotic division.     

Lipids at membrane contact sites: cell signaling and ion transport

Communication between organelles is essential to coordinate cellular functions and the cell's response to physiological and pathological stimuli. Organellar communication occurs at membrane contact sites (MCSs), where the endoplasmic reticulum (ER) membrane is tethered to cellular organelle membranes by specific tether proteins and where lipid transfer proteins and cell signaling proteins are located. MCSs have many cellular functions and are the sites of lipid and ion transfer between organelles and generation of second messengers. This review discusses several aspects of MCSs in the context of lipid transfer, formation of lipid domains, generation of Ca²⁺ and cAMP second messengers, and regulation of ion transporters by lipids.     

Induction and stabilization of synchrony in the cell division of Escherichia coli

Escherichia coli strains B5 and B/r/1 were grown under conditions of periodic glucose starvation in a minimal medium. Such conditions of growth give rise to two synchronous populations that are out of phase regarding their time of division, one dividing shortly after a new supply of fresh medium and the other at a later stage of the feeding cycle. Preferential selection of one of the two populations using heat treatment resulted in a homogeneous synchronized culture that exhibited in a non-limiting medium a high degree of synchrony that was long lasting. Synchrony and its persistence could survive preservation of such a synchronized culture by freeze drying. An explanation of the synchrony persistence was put forward and the practical implications of these findings were discussed.     

Induction of cell division in a temperature-sensitive division mutant of Escherichia coli by inhibition of protein synthesis.

Synchronous cells of the thermosensitive division-defective Escherichia coli strain MACI (divA) divided at the restrictive temperature (42 degrees C) if they were allowed to grow at 42 degrees C for a certain period before protein synthesis was inhibited by adding chloramphenicol (CAP) or rifampicin. The completion of chromosome replication was not required for such divA-independent division. Synchronous cells of strain MACI divided in the presence of an inhibitor of DNA synthesis, nalidixic acid, if they were shifted to 42 degrees C and CAP or rifampicin was added after some time; cells of the parent strain MC6 (div A+) treated in the same way did not divide. These data suggest that coupling of cell division to DNA synthesis depends on the divA function. The ability to divide at 42 degrees C, whether or not chromosome termination was allowed, was directly proportional to the mean cell volume of cultures at the time of CAP addition, suggesting that cells have to be a certain size to divide under these conditions. The period of growth required for CAP-induced division had to be at the restrictive temperature; when cells were grown at 30 degrees C, in the presence of nalidixic acid to prevent normal division, they did not divide on subsequent transfer to 42 degrees C followed, after a period, by protein synthesis inhibition. A model is proposed in which the role of divA as a septation initiator gene is to differentiate surface growth sites by converting a primary unregulated structure, with the capacity to make both peripheral wall and septum, to a secondary structure committed to septum formation.     

Indole prevents Escherichia coli cell division by modulating membrane potential

Indole is a bacterial signalling molecule that blocks E. coli cell division at concentrations of 3-5mM. We have shown that indole is a proton ionophore and that this activity is key to the inhibition of division. By reducing the electrochemical potential across the cytoplasmic membrane of E. coli, indole deactivates MinCD oscillation and prevents formation of the FtsZ ring that is a prerequisite for division. This is the first example of a natural ionophore regulating a key biological process. Our findings have implications for our understanding of membrane biology, bacterial cell cycle control and potentially for the design of antibiotics that target the cell membrane.     

A mechanism of division of a cell with an impermeable membrane

The case of a cell in which metabolites are produced and consumed within the cell, without leaving the cell, is considered. Conditions are given under which there may be an excess production at the center over that at the periphery, and this condition is stable with respect to displacement of the center. The resulting diffusion forces are considered, and an expression is developed for the Rate of elongation with time. The expression is very similar to that obtained by considering the flow of metabolites into and out of the cell.     

Borrelia burgdorferi ftsZ plays a role in cell division

ftsZ is essential for cell division in many microorganisms. In Escherichia coli and Bacillus subtilis, FtsZ plays a role in ring formation at the leading edge of the cell division septum. An ftsZ homologue is present in the Borrelia burgdorferi genome (ftsZ(Bbu)). Its gene product (FtsZ(Bbu)) is strongly homologous to other bacterial FtsZ proteins, but its function has not been established. Because loss-of-function mutants of ftsZ(Bbu) might be lethal, the tetR/tetO system was adapted for regulated control of this gene in B. burgdorferi. Sixty-two nucleotides of an ftsZ(Bbu) antisense DNA sequence under the control of a tetracycline-responsive modified hybrid borrelial promoter were cloned into pKFSS1. This construct was electroporated into a B. burgdorferi host strain carrying a chromosomally located tetR under the control of the B. burgdorferi flaB promoter. After induction by anhydrotetracycline, expression of antisense ftsZ RNA resulted in generation of filamentous B. burgdorferi that were unable to divide and grew more slowly than uninduced cells. To determine whether FtsZ(Bbu) could interfere with the function of E. coli FtsZ, ftsZ(Bbu) was amplified from chromosomal DNA and placed under the control of the tetracycline-regulated hybrid promoter. After introduction of the construct into E. coli and induction with anhydrotetracycline, overexpression of ftsZ(Bbu) generated a filamentous phenotype. This suggested interference of ftsZ(Bbu) with E. coli FtsZ function and confirmed the role of ftsZ(Bbu) in cell division. This is the first report of the generation of a B. burgdorferi conditional lethal mutant equivalent by tetracycline-controlled expression of antisense RNA.