Ran GTPase: a master regulator of nuclear structure and function during the eukaryotic cell division cycle?

Ran is an abundant GTPase that is highly conserved in eukaryotic cells and has been implicated in many aspects of nuclear structure and function, especially determining the directionality of nucleocytoplasmic transport during interphase. However, cell-free systems have recently shown that Ran plays distinct roles in mitotic spindle assembly and nuclear envelope (NE) formation in vitro. During spindle assembly, Ran controls the formation of complexes with importins, the same effectors that control nucleocytoplasmic transport. Here, we review these advances and discuss a general model for Ran in the coordination of nuclear processes throughout the cell division cycle via common biochemical mechanisms.     

The synaptic vesicle cycle: is kissing overrated?

In this issue of Neuron, Granseth et al. re-examine the mechanism of endocytosis at hippocampal synapses using a new optical reporter, sypHy. They conclude that only a single slow mode of endocytosis operates at this synapse and that retrieval after physiological stimuli is largely, if not solely, dominated by the clathrin-mediated pathway. These conclusions dispute previous assertions that "kiss-and-run" is a major mechanism of vesicle recycling at hippocampal synapses.     

How do small GTPase signal transduction pathways regulate cell cycle entry?

A variety of studies have shown that activation of the cell cycle machinery requires the participation of multiple signalling pathways. These pathways include Ras-dependent effectors such as the extracellular-signal related kinases, otherwise known as mitogen-activated protein kinases (ERKs, MAPKs), phosphatidylinositol 3 (PI3)-kinase and p21Ral pathways, as well as other signalling pathways regulated by the small GTPases p21Rho, p21Rac and p21Cdc42.     

The nuclear pore complex: oily spaghetti or gummy bear?

In this issue, Frey and G?rlich (2007) provide new insight into the selective barrier that controls protein traffic through the nuclear pore complex. They show that a single protein domain of the nuclear pore protein Nsp1 can form a hydrogel that allows highly selective access of nuclear transport receptors and their cargos, but rejects other proteins of similar size.     

The nuclear matrix of Euglena gracilis (Euglenophyta): A stage of nuclear matrix evolution?

Euglena gracilis cell was extracted sequentially with CSK-Triton buffer, RSB-Magik solution and DNase-As solution. DGD embedment-free electron microscopy showed that in the extracted nucleus there was a residual non-chromatin fibrous network. That it could not be removed by hot trichloroacetic acid further supported the idea that it was a non-histone, non-chromatin fibrous protein network, and should be the internal network of the nuclear matrix. After the sequential extraction, the nuclear membrane was removed, leaving behind a layer of lamina; the chromatin was digested and eluted from the dense chromosomes and residual chromosomal structures that should be chromosomal scaffold were revealed. Western blot analysis with antiserum against rat lamins showed that nuclear lamina of the cell possessed two positive polypeptides, a major one and a minor one, which had molecular masses similar to lamin B and lamin A, respectively. Comparing these data with those of the most primitive eukaryote Archezoa and of higher eukaryotes, it was suggested that the lower unicellular eukaryote E. gracilis already had the nuclear matrix structure, and its nuclear matrix (especially the lamina) might represent a stage of evolutionary history of the nuclear matrix.     

The carbon cycle on early Earth--and on Mars?

One of the goals of the present Martian exploration is to search for evidence of extinct (or even extant) life. This could be redefined as a search for carbon. The carbon cycle (or, more properly, cycles) on Earth is a complex interaction among three reservoirs: the atmosphere; the hydrosphere; and the lithosphere. Superimposed on this is the biosphere, and its presence influences the fixing and release of carbon in these reservoirs over different time-scales. The overall carbon balance is kept at equilibrium on the surface by a combination of tectonic processes (which bury carbon), volcanism (which releases it) and biology (which mediates it). In contrast to Earth, Mars presently has no active tectonic system; neither does it possess a significant biosphere. However, these observations might not necessarily have held in the past. By looking at how Earth's carbon cycles have changed with time, as both the Earth's tectonic structure and a more sophisticated biology have evolved, and also by constructing a carbon cycle for Mars based on the carbon chemistry of Martian meteorites, we investigate whether or not there is evidence for a Martian biosphere.     

HU: promoting or counteracting DNA compaction?

The role of HU in Escherichia coli as both a protein involved in DNA compaction and as a protein with regulatory function seems to be firmly established. However, a critical look at the available data reveals that this is not true for each of the proposed roles of this protein. The role of HU as a regulatory or accessory protein in a number of systems has been thoroughly investigated and in many cases has been largely elucidated. However, almost 30 years after its discovery, convincing evidence for the proposed role of HU in DNA compaction is still lacking. Here we present an extensive literature survey of the available data which, in combination with novel microscopic insights, suggests that the role of HU could be the opposite as well. The protein is likely to play an architectural role, but instead of being responsible for DNA compaction it could be involved in antagonising compaction by other proteins such as H-NS.     

The glyoxylate cycle: does it function in the dormant or active bear?

The presence of or induction of an active glyoxylate cycle (GC) in the dormant black bear whose sole source of energy is body fat is an attractive concept which would allow lipid (acetate) to be directed from oxidation via the tricarboxylic acid cycle to many biosynthetic pathways. However, in spite of earlier claims, the present report establishes that isocitrate lyase and malate synthetase, GC marker enzymes, could not be detected in liver or kidney of active or dormant bears; liver peroxisome numbers were similar. The absence of brown fat (by light microscopy) and of the GC enzymes in the dormant bear raises questions about the prior report.     

The sylvatic cycle of Neospora caninum: where do we go from here?

Bovine abortions due to Neospora caninum infection are a major cattle-production problem worldwide. The parasite is readily maintained in cattle populations by vertical transmission. The domestic dog excretes oocysts in its feces and, after sporulation, these oocysts are infectious to cattle. Current control measures are aimed at culling infected cows and limiting the access of cattle to infective oocysts. The recent revelations that coyotes (Canis latrans) can excrete N. caninum oocysts in their feces and that white-tailed deer (Odocoileus virginianus) are natural intermediate hosts of the parasite demonstrate the existence of a sylvatic cycle of neosporosis in North America. This complicates parasite-prevention programs but opens many new and exciting avenues of research. Similar canid-ruminant sylvatic cycles might exist in other countries and, if so, need to be investigated.     

TBC proteins: GAPs for mammalian small GTPase Rab?

The TBC (Tre-2/Bub2/Cdc16) domain was originally identified as a conserved domain among the tre-2 oncogene product and the yeast cell cycle regulators Bub2 and Cdc16, and it is now widely recognized as a conserved protein motif that consists of approx. 200 amino acids in all eukaryotes. Since the TBC domain of yeast Gyps [GAP (GTPase-activating protein) for Ypt proteins] has been shown to function as a GAP domain for small GTPase Ypt/Rab, TBC domain-containing proteins (TBC proteins) in other species are also expected to function as a certain Rab-GAP. More than 40 different TBC proteins are present in humans and mice, and recent accumulating evidence has indicated that certain mammalian TBC proteins actually function as a specific Rab-GAP. Some mammalian TBC proteins {e.g. TBC1D1 [TBC (Tre-2/Bub2/Cdc16) domain family, member 1] and TBC1D4/AS160 (Akt substrate of 160 kDa)} play an important role in homoeostasis in mammals, and defects in them are directly associated with mouse and human diseases (e.g. leanness in mice and insulin resistance in humans). The present study reviews the structure and function of mammalian TBC proteins, especially in relation to Rab small GTPases.     

The life cycle of Reticulitermes spp (Isoptera: Rhinotermitidae): what do we know?

The subterranean termites in the genus Reticulitermes have a complex and plastic life cycle, which has been the subject of a number of publications over the past century. Given the inherent difficulties in studying such cryptic, eusocial organisms it is not perhaps surprising that the literature on their biology has failed to reach a consensus. An overview of the literature is given, which is followed by a discussion of the various theories on the life cycle of Reticulitermes spp. A substantial proportion of the review focuses on the French literature, which constitutes the majority of the primary sources and can be difficult to access. There are many discrepancies in the literature in terms of the number of instars, the definition of workers and the question of whether they should be termed pseudergates or, potentially, an additional terminology used to differentiate between pseudergates and the true workers seen in the higher termites (Isoptera: Termitidae). It remains very difficult to compare publications as there is little conformity; a problem that is aggravated by a general absence of drawings of the relevant instars. Further work on the biology of Reticulitermes is clearly required. There is also a need for researchers to agree on a standard terminology for this genus. A glossary is provided for the various synonyms and definitions.     

The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched?

The flexibility displayed by apicomplexan parasites to vary their mode of replication has intrigued biologists since their discovery by electron microscopy in the 1960s and 1970s. Starting in the 1990s we began to understand the cell biology of the cytoskeleton elements driving cytokinesis. By contrast, the molecular mechanisms that regulate the various division modes and how they translate into the budding process that uniquely characterizes this parasite family are much less understood. Although growth mechanisms are a neglected area of study, it is an important pathogenic parameter as fast division rounds are associated with fulminant infection whereas slower growth attenuates virulence, as is exploited in some vaccine strains. In this review we summarize a recent body of cell biological experiments that are rapidly leading to an understanding of the events that yield successful mitosis and cytokinesis in Toxoplasma. We place these observations within a cell cycle context with comments on how these events may be regulated by known eukaryotic checkpoints active in fission and budding yeasts as well as mammalian cells. The presence of cell cycle control mechanisms in the Apicomplexa is supported by our findings that identify several cell cycle checkpoints in Toxoplasma. The progress of the cell cycle is ultimately controlled by cyclin-Cdk pair activities, which are present throughout the Apicomplexa. Although many of the known controllers of cyclin-Cdk activity are present, several key controls cannot readily be identified, suggesting that apicomplexan parasites deviate at these points from the higher eukaryotic models. Altogether, new insights in Toxoplasma replication are reciprocally applied to hypothesize how other division modes in the Toxoplasma life cycle and in other Apicomplexa species could be controlled in terms of cell cycle checkpoint regulation.     

The kidney form of Trypanosoma musculi: A distinct stage in the life cycle?

Trypanosoma musculi is a parasite specific to mice, which resides in the blood and lacks intracellular stages. After immune clearance of the flagellates from the general circulation, mice are resistant to reinfection. Yet, long after parasites are no longer detected in the peripheral blood, they persist in the vasa recta of the kidneys and it has been proposed that this is an immunologically privileged site for T. musculi. This relationship provides a useful model for studies of latent or chronic infections in immune hosts. Here, Fernando Monroy and Donald Dusanic consider the immune responses of mice to T. musculi and compare characteristics of the parasites from the vasa recta (kidney forms, KFs) of mice with latent infections to trypanosomes from the peripheral blood (bloodstream forms, BSFs) of animals during active infections. They consider how KFs evade immune destruction and suggest that these sequestered parasites represent a distinct stage in the life cycle.     

The circadian cycle: is the whole greater than the sum of its parts?

The term 'circadian rhythm' describes an oscillatory behavior in the absence of exogenous environmental cues, with a period of about a day. As yet, we don't fully understand which biological mechanisms join together to supply a stable and self-sustained oscillation with such a long period. By chipping away at the molecular mechanism with genetic approaches, some common features are emerging. In combining molecular analyses and physiological experiments, those features that are crucial for structuring a circadian day could be uncovered.