Cilia and the cell cycle?

A recent convergence of data indicating a relationship between cilia and proliferative diseases, such as polycystic kidney disease, has revived the long-standing enigma of the reciprocal regulatory relationship between cilia and the cell cycle. Multiple signaling pathways are localized to cilia in mammalian cells, and some proteins have been shown to act both in the cilium and in cell cycle regulation. Work from the unicellular alga Chlamydomonas is providing novel insights as to how cilia and the cell cycle are coordinately regulated.     

What befalls the proteins and water in a living cell when the cell dies?

The solvency of solutes of varying molecular size in the intracellular water of freshly-killed Ehrlich carcinoma cells fits the same theoretical curve that describes the solvency of similar solutes in a 36% solution of native bovine hemoglobin--a protein found only in red blood cells and making up 97.3% of the red cell's total intracellular proteins. The merging of the two sets of data confirms the prediction of the AI Hypothesis that key intracellular protein(s) in dying cells undergo(es) a transition from: (1) one in which the polypeptide NHCO groups assume a fully-extended conformation with relatively strong power of polarizing and orienting the bulk-phase water in multilayers; to (2) one in which most of the polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformations (see below for definition) with much weaker power in polarizing-orienting multilayers of bulk-phase water. This concordance of the two sets of data also shows that what we now call native hemoglobin--supposedly denoting hemoglobin found in its natural state in living red blood cells--, in fact, more closely resembles the water-polarizing, and -orienting intracellular proteins in dead cells. Although in the dead Ehrlich carcinoma cells as well as in the 36% solution of native hemoglobin, much of the protein's polypeptide NHCO groups are engaged in alpha-helical and other "introvert" conformation (Perutz 1969; Weissbluth 1974), both systems produce a weak but nonetheless pervasive and "long-range" water polarization and orientation. It is suggested that in both the dead Ehrlich carcinoma ascites cells and in the 36% native bovine hemoglobin solution, enough polypeptide NHCO groups assume the fully-extended conformation to produce the weak but far-reaching multilayer water polarization and orientation observed.     

Cell–cell contact and signaling in the muscle stem cell niche

Muscle stem cells (also called satellite cells or SCs) rely on their local niche for regulatory signals during homeostasis and regeneration. While a number of cell types communicate indirectly through secreted factors, here we focus on the significance of direct contact between SCs and their neighbors. During quiescence, SCs reside under a basal lamina and receive quiescence-promoting signals from their adjacent skeletal myofibers. Upon injury, the composition of the niche changes substantially, enabling the formation of new contacts that mediate proliferation, self-renewal, and differentiation. In this review, we summarize the latest work in understanding cell–cell contact within the satellite cell niche and highlight areas of open questions for future studies.     

When and how does cell division order influence cell allocation to the inner cell mass of the mouse blastocyst?

Aggregate 8-cell embryos were constructed from four 2/8 pairs of blastomeres, one of which was marked with a short-term cell lineage marker and was also either 4 h older (derived from an early-dividing 4-cell) or 4 h younger (derived from a late-dividing 4-cell) than the other three pairs. The aggregate embryos were cultured to the 16-cell stage, at which time a second marker was used to label the outside cell population. The embryos were then disaggregated and each cell was examined to determine its labelling pattern. From this analysis, we calculated the relative contributions to the inside cell population of the 16-cell embryo of older and younger cells. Older cells were found to contribute preferentially. However, if the construction of the aggregate 8-cell embryo was delayed until each of the contributing 2/8 cell pairs had undergone intercellular flattening and then had been exposed to medium low in calcium to reverse this flattening immediately prior to aggregation, the advantage possessed by the older cells was lost. These results support the suggestion that older cells derived from early-dividing 4-cell blastomeres contribute preferentially to the inner cell mass as a result of being early-flattening cells.     

Diabetes mellitus and the β cell: the last ten years

Diabetes is a major global problem. During the past decade, the genetic basis of various monogenic forms of the disease, and their underlying molecular mechanisms, have been elucidated. Many genes that increase type 2 diabetes (T2DM) risk have also been identified, but how they do so remains enigmatic. Nevertheless, defective insulin secretion emerges as the main culprit in both monogenic and polygenic diabetes, with environmental and lifestyle factors, via obesity, accounting for the current dramatic increase in T2DM. There also have been significant advances in therapy, particularly for some monogenic disorders. We review here what ails the β cell and how its function may be restored.     

Characterization of Giardia cell nucleus：Its implication on the nature and origin of the primitive cell nucleus

Thecentralproblemoftheoriginandearlyevolutionoftheeukaryoticcel1istheoriginofthecellnucleus,becausethecellnucleus,withitsdouble-layerednuclearenvelope,isthemostprominentandimportantmorphologicalmarkdistinguishingeukaryoticcellsfromprokaryotes.Eukaryoticcellsmayhavenochloroplast,mito-chondriaorflagellum,buttheymustpossessacellnucleus.Thecellnucleusitselfisaverycomplicatedstructure-Ifwetrytomakecleartheoriginandearlyevolutionofthecellnucleus,weoughttoinvestigatetheoriginandevolutionofeachmorphol…     

Effect of theβ-d-galactoside-binding lectin on cell to substratum and cell to cell adhesion of cells from the extraembryonic endoderm of the early chick blastoderm

Summary Cells from the extraembryonic endoderm of the gastrulating chick embryo contain a -d-galactoside-binding lectin inhibited by thiodigalactoside (TDG). When cell suspensions are cultured in stationary culture in the presence of exogenously added purified blastoderm lectin or TDG, their attachment to the substratum is delayed and decreased compared to controls. The cells take on a fibroblastic-like morphology and cell to cell contact becomes limited to localized areas of the cell surface. Many lectin or TDG-treated cells appear to be migrating over the substratum. This is in contrast to control cultures where the cells appear epithelial in morphology and tend to maximize their areas of apposition. These data suggest that the endogenous lectin may have a role to play in cell to substratum and cell to cell adhesion.     

The extrinsic cell death pathway and the élan mortel

Early in the exploration of the chemical nature of life, it was widely believed that the molecules of living organisms, by their very nature, differ from those of inorganic material molecules and possess a vital force ('élan vital'). Similarly, early scientific thinking on the subject of cell death and its induction by cytotoxic cells of the immune system was pervaded by a sense that the molecules mediating these functions possess intrinsic deadly activity and are dedicated exclusively to death-related tasks. This impression was also reflected in the initial notions of the mode of action of intracellular proteins that signal for death. It is now gradually becoming clear, however, that proteins participating in death induction also have functions unrelated to death. Nevertheless, as exemplified by studies of the function of caspase-8 (an enzyme that signals both for activation of the extrinsic cell-death pathway and for non-death-related effects), analysis of the mechanistic basis for such heterogeneity might allow identification of distinct structural determinants in the proteins participating in death induction that do bear death specificity.Cell Death and Differentiation (2008) 15, 1533-1541; doi:10.1038/cdd.2008.41.     

Intercellular variation in signaling through the TGF-β pathway and its relation to cell density and cell cycle phase

Fundamental open questions in signal transduction remain concerning the sequence and distribution of molecular signaling events among individual cells. In this work, we have characterized the intercellular variability of transforming growth factor β-induced Smad interactions, providing essential information about TGF-β signaling and its dependence on the density of cell populations and the cell cycle phase. By employing the recently developed in situ proximity ligation assay, we investigated the dynamics of interactions and modifications of Smad proteins and their partners under native and physiological conditions. We analyzed the kinetics of assembly of Smad complexes and the influence of cellular environment and relation to mitosis. We report rapid kinetics of formation of Smad complexes, including native Smad2-Smad3-Smad4 trimeric complexes, in a manner influenced by the rate of proteasomal degradation of these proteins, and we found a striking cell to cell variation of signaling complexes. The single-cell analysis of TGF-β signaling in genetically unmodified cells revealed previously unknown aspects of regulation of this pathway, and it provided a basis for analysis of these signaling events to diagnose pathological perturbations in patient samples and to evaluate their susceptibility to drug treatment.     

Computational modelling and analysis of mechanical conditions on cell locomotion and cell–cell interaction

Between other parameters, cell migration is partially guided by the mechanical properties of its substrate. Although many experimental works have been developed to understand the effect of substrate mechanical properties on cell migration, accurate 3D cell locomotion models have not been presented yet. In this paper, we present a novel 3D model for cells migration. In the presented model, we assume that a cell follows two main processes: in the first process, it senses its interface with the substrate to determine the migration direction and in the second process, it exerts subsequent forces to move. In the presented model, cell traction forces are considered to depend on cell internal deformation during the sensing step. A random protrusion force is also considered which may change cell migration direction and/or speed. The presented model was applied for many cases of migration of the cells. The obtained results show high agreement with the available experimental and numerical data.     

γ-Actin regulates cell migration and modulates the ROCK signaling pathway

Cell migration plays a crucial role in numerous cellular functions, and alterations in the regulation of cell migration are required for invasive transformation of a tumor cell. While the mechanistic process of actin-based migration has been well documented, little is known as to the specific function of the nonmuscle actin isoforms in mammalian cells. Here, we present a comprehensive examination of γ-actin's role in cell migration using an RNAi approach. The partial suppression of γ-actin expression in SH-EP neuroblastoma cells resulted in a significant decrease in wound healing and transwell migration. Similarly, the knockdown of γ-actin significantly reduced speed of motility and severely affected the cell's ability to explore, which was, in part, due to a loss of cell polarity. Moreover, there was a significant increase in the size and number of paxillin-containing focal adhesions, coupled with a significant decrease in phosphorylated paxillin in γ-actin-knockdown cells. In addition, there was a significant increase in the phosphorylation of cofilin and myosin regulatory light chain, suggesting an overactivated Rho-associated kinase (ROCK) signaling pathway in γ-actin-knockdown cells. The alterations in the phosphorylation of paxillin and myosin regulatory light chain were unique to γ-actin and not β-actin knockdown. Inhibition of the ROCK pathway with the inhibitor Y-27632 restored the ability of γ-actin-knockdown cells to migrate. This study demonstrates γ-actin as a potential upstream regulator of ROCK mediated cell migration.     

Plasmid replication and partition in Escherichiacoli: is the cell membrane the key?

The DNA–membrane complex has been the subject of intensive investigation for over 35 years as the possible site for DNA replication in the prokaryotic cell and the site through which newly synthesized chromosomes are segregated into daughter cells. However, the molecular mechanisms which control these phenomena are, for the most part, poorly understood despite genetic, biochemical, and morphologic evidence in favour of their existence. This is probably due to the transient nature and non-covalent interactions that occur between DNA and the membrane. In addition, there is a paucity of knowledge concerning the nature of the membrane receptors for DNA and whether the membrane plays simply a structural or metabolic role in the two processes. Plasmids can provide important insights into the role of the membrane in replication and partitioning because the plasmid life cycle is relatively simple, with replication occurring during the cell cycle and partitioning during cell division. The replicon model of Jacob et al. (1963, Cold Spring Harbor Symp Quant Biol 28: 329–348) still represents a good conceptual framework (with modifications) to explain how plasmid replication and partitioning are linked by the membrane. In its simplest form, the model focuses on specific membrane binding sites (possibly along the equator of the cell) for plasmid (or bacterial) replication, with the membrane acting as a motive force to separate the newly synthesized replicons and their attached sites into daughter cells. Indeed, proteins involved in both plasmid replication and partitioning have been found in membrane fractions and some plasmids require membrane binding for initiation and an active partitioning. We propose that several factors are critical for both plasmid DNA replication and partitioning. One factor is the extent of negative supercoiling (brought about by an interplay of various topoisomerases, but most importantly by DNA gyrase). Supercoiling is known to be critical for initiation of DNA replication but may also be important for the formation of a partition complex in contact with the cell membrane. Another factor is the presence of specific subdomains of the membrane which can interact specifically with origin DNA and possibly other regions involved in partitioning. Such domains may be induced transiently or be present at all times during the cell cycle.