Dispatch. Cell division: the place and time of cytokinesis

Recent studies have provided evidence that, during cytokinesis, activation of the Pbl-Rho1 pathway by a protein complex located at the spindle midzone, and inhibition of this pathway by two mitotic cyclins, may be major contributing factors controlling the place and timing of the cleavage furrow.     

FtsZ and bacterial cell division

In this review we describe proteins and supermolecular structures which take part in the division of bacterial cells. FtsZ, a eukaryotic tubulin homolog is a key cell division protein in most prokaryotes. FtsZ, as well as tubulin, is capable of binding and hydrolyzing GTP. The division of a bacterial cell begins with the forming of a so-called divisome. The basis of such a divisome is a contractile ring (Z ring) which encircles the cell about midcell. The Z-ring consists of a bundle of laterally bound protofilaments formed in result of FtsZ polymerization. Z-ring is rigidly bounded to the cytosolic side of the inner membrane with the participation of FtsA, ZipA, FtsW and many other divisome cell division proteins. The ring directs the process of cytokinesis transmitting constriction power to the membrane. The primary structures of the prokaryotic FtsZ family members significantly differ from eukaryotic tubulins except for the sites of GTP binding. There is a high degree of structural homology between these proteins in the region. FtsZ is one of the most conserved proteins in prokaryotes. However, ftsZ genes have not been found in several species of microorganisms with completely sequenced genomes. They include two species of mycoplasmas (Ureaplasma parvum and Mycoplasma mobile), Prostecobacter dejongeii, 10 species of chlamydia and 5 species of archaea. Consequently, these organisms divide without FtsZ participation. The genomes of U. parvum and M. mobile have many open reading frames which encode proteins with unknown functions. A comparison of the primary structures of these hypothetical proteins did not identify any known cell division proteins. We hypothesize that the process of cell division in these organisms should involve proteins similar to FtsZ in function and homologous to FtsZ or other cell division proteins in structure.     

Cortical neuron specification: it has its time and place

Cortical neurogenesis is a highly stereotyped process in which progenitor cells generate neurons destined for specific cortical layers depending on the timing of cell cycle exit. Previous work has shown that during corticogenesis, progenitors become progressively restricted in their developmental potential. Recent work has uncovered some of the intrinsic mechanisms that underlie this fate restriction. In addition to timing, new studies suggest that the location of cell cycle exit in the cortical germinal zone may also contribute to cortical neuron specification.     

Mitosis: regulation and organization of cell division

Modern views on genetic, cytological and molecular bases of the structure and regulation of preparing and implementing mitotic chromosome segregation are discussed.     

Nucleoid occlusion and bacterial cell division

The bacterial cell cycle requires the tight regulation and precise coordination of several sophisticated cellular processes. Prominent among them is the formation of the dividing wall or septum, which has to take place at the right time and place to ensure equality of the progeny and integrity of the genome. Nucleoid occlusion is a defence mechanism that prevents the chromosome from being bisected and broken by the division septum. It does so by preventing Z ring formation near the nucleoid, which also helps to determine the location of septation.     

FtsZ and the division of bacterial cell

In this review we have tried to describe proteins and supermolecular structures which take part in the division of bacterial cell. The principal cell division protein of the most of prokaryotes is FtsZ, a homologue of eukaryotic tubulin. FtsZ just as tubulin is capable to bind and hydrolyze GTP. The division of bacterial cell begins with forming of so called divisome. The basis of such divisome is a contractile ring (Z ring); the ring encircles the cell about midcell. Z ring consists of a bundle of laterally bound protofilaments, which have been formed as a result of FtsZ polymerization. Z ring is rigidly bounded to cytozolic side of inner membrane with participation of FtsA, ZipA, FtsW and many other cell division proteins of divisome. The ring directs the process of cytokinesis transmitting power of constriction to membrane. Primary structures of members of the family of prokaryotic FtsZs differ from eukaryotic tubulines significantly except the region, where the site of GTP binding is placed. There is high degree of homology between structures of these proteins in the region. FtsZ is one of the most conservative proteins in prokaryotes, but ftsZ genes have not been found in completely sequenced genomes of several species of microorganisms. There are 2 species of mycoplasmas (Ureaplasma parvum and Mycoplasma mobile), Prostecobacter dejongeii, 10 species of chlamydia and 5 species of archaea among them. So these organisms divide without FtsZ. There are many open reading frames which encode proteins with unknown functions in genomes of U. parvum and M. mobile. The comparison of primary structures of these hypothetical proteins with structures of cell division proteins did not allow researchers to find similar proteins among them. We suppose that the process of cell division of these organisms should recruit proteins with function similar to FtsZ and having homologous with FtsZ or other cell division proteins spatial structures.     

The bacterial cell cycle: DNA replication, nucleoid segregation, and cell division

Data on the bacterial cell cycle published in the last 10-15 years are considered, with a special stress on studies of nucleoid segregation between dividing cells. The degree of similarity between the eukaryotic mitotic apparatus and the apparatus performing nucleoid separation is discussed.     

Chromokinesins: localization-dependent functions and regulation during cell division

The bipolar spindle is a highly dynamic structure that assembles transiently around the chromosomes and provides the mechanical support and the forces required for chromosome segregation. Spindle assembly and chromosome movements rely on the regulation of microtubule dynamics and a fine balance of forces exerted by various molecular motors. Chromosomes are themselves central players in spindle assembly. They generate a RanGTP gradient that triggers microtubule nucleation and stabilization locally and they interact dynamically with the microtubules through motors targeted to the chromatin. We have previously identified and characterized two of these so-called chromokinesins: Xkid (kinesin 10) and Xklp1 (kinesin 4). More recently, we found that Hklp2/kif15 (kinesin 12) is targeted to the chromosomes through an interaction with Ki-67 in human cells and is therefore a novel chromokinesin. Hklp2 also associates with the microtubules specifically during mitosis, in a TPX2 (targeting protein for Xklp2)-dependent manner. We have shown that Hklp2 participates in spindle pole separation and in the maintenance of spindle bipolarity in metaphase. To better understand the function of Hklp2, we have performed a detailed domain analysis. Interestingly, from its positioning on the chromosome arms, Hklp2 seems to restrict spindle pole separation. In the present review, we summarize the current knowledge of the function and regulation of the different kinesins associated with chromosome arms during cell division, including Hklp2 as a novel member of this so-called chromokinesin family.     

Genomic channeling in bacterial cell division

The bacterial dcw cluster is a group of genes involved in cell division and peptidoglycan synthesis. Comparison of the cluster across several bacterial genomes shows that its gene content and its gene order are conserved in distant bacterial lineages and, moreover, that, being most conserved in rod-shaped bacteria, the degree of conservation relates to bacterial morphology. We propose a model in which the selective pressure to maintain the cluster arises from the need to efficiently coordinate the processes of elongation and septation in rod-shaped bacteria. Gene order in the dcw cluster would be conserved as a result of mechanisms comprising: (i) a limited amount of peptidoglycan precursors required both for septation and elongation of the wall; (ii) co-translational assembly of the protein complexes involved in cell division and in the synthesis of the peptidoglycan precursors; and (iii) alternation in the cellular localization of the assembled complexes to participate either in the synthesis of the septal peptidoglycan and division, or in the synthesis of the lateral wall. The name genomic channeling is proposed for this model as it involves a genomic arrangement that could facilitate the assembly of specific protein complexes and their subsequent conveyance to specific locations in the crowded cytoplasm and the envelope.     

The great divide: coordinating cell cycle events during bacterial growth and division

The relationship between events during the bacterial cell cycle has been the subject of frequent debate. While early models proposed a relatively rigid view in which DNA replication was inextricably coupled to attainment of a specific cell mass, and cell division was triggered by the completion of chromosome replication, more recent data suggest these models were oversimplified. Instead, an intricate set of intersecting, and at times opposing, forces coordinate DNA replication, cell division, and cell growth with one another, thereby ensuring the precise spatial and temporal control of cell cycle events.     

A two-channel hypothesis for regulation of cell division and differentiation

We propose the hypothesis that extracellular regulation of cell division and differentiation acts through just two communications channels. These channels consist of a series of redundant components: extracellular messenger hormones; these hormones' receptors; cytoplasmic proteins activated by the hormone-receptor complex; and trans-activating nuclear regulatory proteins. One channel, here labeled "D" ("differentiate"), includes transforming growth factor-beta as one of its hormones; the other, labeled "G" ("growth") includes epidermal growth factor. We postulate that signal reception occurs as a result of competition between different actuating proteins for equilibrium-controlled binding to critical DNA sites. Stem cells commit to mitosis when some high proportion of critical sites is occupied by actuating proteins of the G class, and to terminal differentiation when a high proportion is occupied by "D" actuators. Intermediate occupancy can either lead to division into one differentiated and one stem cell, or to maintenance of cells in the reference state, quiescence. Equilibrium control of binding implies that critical site occupancy will be proportional to the relative concentrations of "D" and "G" actuating proteins in the nuclear fluid. These concentrations depend on the external hormone concentrations, the numbers of receptors on the cell membrane, and the coefficients of the rate-determining steps between internalization of the hormone-receptor complexes and activation of the actuating proteins. All of these quantities can be affected by various factors, including endocrine hormones. This model is consistent with most reported behavior of various growth factors, interferons, etc, toward a variety of cells in culture. It predicts that under otherwise constant conditions, high relative concentrations of a D-hormone (e.g. transforming growth factor-beta) will induce commitment to terminal differentiation, while high relative concentrations of a "G" hormone (e.g. epidermal growth factor) will induce mitosis. We have seen no report of an experiment which adequately tests this prediction. The model implies that cancer causing mutations are those which increase the relative intensity of the "G" signal; this can occur via changes in components of either channel. Such mutant cells should be both more likely to divide and less likely to differentiate than normal stem cells. Conversely, mutations which increase relative sensitivity to the "D" signal during embryonal development can lead to premature differentiation, cessation of growth, and structural abnormalities (terata).     

The polymerization mechanism of the bacterial cell division protein FtsZ

Translin and Trax are components of an RNA binding complex initially detected in extracts of brain and testes. Although other tissues appear to contain much lower or negligible levels of the Translin/Trax gel-shift complex, we found, unexpectedly, that several of these peripheral tissues express Translin and Trax proteins at levels comparable to those present in brain. In this study, we demonstrate that the paradoxically low levels of the Translin/Trax complex in kidney and other peripheral tissues are due to masking of these sites by endogenous RNA. Thus, these findings indicate that the Translin/Trax complex is involved in RNA processing in a broader range of tissues than previously recognized.