Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?

Adult CNS neurons are typically described as permanently postmitotic but there is probably nothing permanent about the neuronal cell cycle arrest. Rather, it appears that these highly differentiated cells must constantly keep their cell cycle in check. Relaxation of this vigilance leads to the initiation of a cell cycle and entrance into an altered and vulnerable state, often leading to death. There is evidence that neurons which are at risk of neurodegeneration are also at risk of re-initiating a cell cycle process that involves the expression of cell cycle proteins and DNA replication. Failure of cell cycle regulation might be a root cause of several neurodegenerative disorders and a final common pathway for others.     

Universal cell cycle regulation?

The mechanisms that couple the control of initiation of chromosome replication and cell division to the mass increase of a growing cell are not understood. Here, models are considered in which replication and division are controlled through signals generated by completion of different morphological steps during cell cycle progression.     

Life cycle abbreviation in trematode parasites and the developmental time hypothesis: is the clock ticking?

The typical multi‐host life cycle of many parasites, although conferring several advantages, presents the parasites with a highly hazardous transmission route. As a consequence, parasites have evolved various adaptations increasing their chances of transmission between the different hosts of the life cycle. Some trematode species like the opecoelid Coitocaecum parvum have adopted a more drastic alternative strategy whereby the definitive host is facultatively dropped from the cycle, resulting in a shorter, hence easier to complete, life cycle. Like other species capable of abbreviating their life cycle, C. parvum does so through progenetic development within its intermediate host. Laboratory‐reared C. parvum can modulate their developmental strategy inside the second intermediate host according to current transmission opportunities, though this ability is not apparent in natural C. parvum populations. Here we show that this difference is likely due to the time C. parvum individuals spend in their intermediate hosts in the natural environment. Although transmission opportunities, i.e. chemical cues of the presence of definitive hosts, promoted the adoption of a truncated life cycle in the early stages of infection, individuals that remained in their amphipod host for a relatively long time had a similar probability of adopting progenesis and the abbreviated cycle, regardless of the presence or absence of chemical cues from the predator definitive host. These results support the developmental time hypothesis which states that parasites capable of facultative life cycle abbreviation should eventually adopt progenesis regardless of transmission opportunities, and provide further evidence of the adaptive plasticity of parasite transmission strategies.     

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.     

Time perception: brain time or event time?

Recent experiments show that synchronous events can appear to an observer to occur at different times. Neural processing time delays are offered as an explanation of these temporal illusions, but equating perceived time with processing time leads to some thorny philosophical problems.     

A time to divide: does the circadian clock control cell cycle?

A variety of molecular, genomic and epidemiological evidence has linked cell cycle regulation to circadian rhythms. In a recent issue of Molecular Cell, Koeffler and colleagues show that PER1 sensitizes human cancer cells to ionizing radiation-induced apoptosis. In addition, PER1 expression was found to be downregulated in human tumors, suggesting a tumor suppressor role for the PER1 protein. The significance of PERs, clocks, and cell cycle control is discussed.     

Density regulation during the regeneration of two monocarpic bamboos: self-thinning or intraclonal regulation?

Abstract. The population dynamics of two monocarpic bamboos, Sasa kurilensis and S. tsuboiana, were studied for more than 10 years after establishment following mass flowering. Both species show vigorous rhizomatous vegetative reproduction after growing up to maturity, but horizontal expansion in the seedling stage was much more vigorous in S. tsuboiana than in S. kurilensis. The pattern of changes in culm density in the two species was strikingly similar: culm densities of both species increased until they reached full-density states, after which they decreased in accordance with seedling growth. However, the mode of regulation in culm density was different. S. kurilensis seedlings were composed of only a few culms and scarcely extended their rhizomes during the observation period. Such poor lateral expansion resulted in asymmetric competition as observed in many non-clonal plants, and consequently their culm density decreased as a result of the mortality of genets due to self-thinning. In S. tsuboiana seedlings, the number of culms per genet increased considerably by frequent tillering and sprouting from rhizomes. However, after reaching full density state, the Bud Utility Ratio (BUR), (the proportion of the rhizome nodes with culms to the total number of rhizome nodes), decreased drastically. In this manner, S. tsuboiana regulated culm density intraclonally as is observed in the stable states of many clonal plants. Hence it is important for the understanding of the regeneration process in clonal species to clarify when and how their seedlings extend rhizomes during their growth.     

Exosomes and retroviruses: the chicken or the egg?

Retroviruses appropriate pre‐existing cellular machineries to propagate. In the last decade, impressive similarities have been observed in the generation and dissemination in the host cells of retroviruses and small cellular vesicles known as exosomes. These cellular vesicles are thought to facilitate intercellular communication processes and mediate immune functions. However, their link to the retroviral life cycle has given rise to distinct hypotheses and puzzling dilemmas. Are exosomes the antecessors of retroviruses or do retroviruses merely exploit the same cellular machinery designated for exosome biosynthesis? Here, we address these fascinating evolutionary questions by reviewing recent discoveries and analysing the controversies surrounding them.     

Feeding by coral reef mesograzers: algae or cyanobacteria?

Marine studies on herbivory have addressed the role of algae as food and shelter for small consumers, but the potential of benthic cyanobacteria to play similar roles is largely unknown. Here, feeding preferences were measured for eight invertebrate consumers from Guam, offered four common macroalgae and two cyanobacteria. The survivorship of another consumer raised on either macroalgae or cyanobacteria was also assessed. From the choices offered, the sacoglossans Elysia rufescens and E. ornata consumed the green macroalga Bryopsis pennata. The crab Menaethius monoceros preferred the red alga Acanthophora spicifera. The amphipods Parhyale hawaiensis and Cymadusa imbroglio consumed macroalgae and cyanobacteria in equivalent amounts, with C. imbroglio showing less selectivity among diets. In contrast to these patterns, in these assays the gastropods Stylocheilus striatus, Haminoea cymbalum, H. ovalis, and Haminoea sp. fed exclusively, or survived only, on cyanobacteria. Preferences for different cyanobacteria varied. Field surveys of cyanobacteria-associated species yielded 34 different invertebrate taxa and suggested different degrees of specificity in these associations. Tropical mesograzers exploit considerably different food resources, with some species adapted to consume cyanobacterial mats. Benthic cyanobacteria may play important roles as food and shelter for marine consumers and may indirectly influence local biodiversity through their associated fauna.     

Hyperglycemia and glucosamine-induced mesangial cell cycle arrest and hypertrophy: Common or independent mechanisms?

The Hexosamine Pathway (HP) is one hypothesis proposed to explain glucose toxicity and the alterations observed during the course of diabetic microvascular complication development. Glucosamine is a precursor of UDP-N-Acetylglucosamine (UDP-GlcNAc), the main product of the HP that has often been used to mimic its activation. The transfer of a UDP-GlcNAc residue onto proteins (O-GlcNAc modification) represents the final step of the HP and is considered as a major mechanism by which this pathway exerts its signalling effects. While it is well accepted that the HP promotes extracellular matrix accumulation in the context of diabetic nephropathy, its involvement in the perturbations of cell cycle progression and hypertrophy of renal cells has been poorly investigated. Nevertheless, in a growing number of studies, the HP and O-GlcNAc modification are emerging as important regulators of cell cycle progression. This review will focus on the role of glucosamine and O-GlcNAc modification in cell cycle regulation in the context of diabetic nephropathy. Special emphasis will be given into the role of the HP as a potential mediator of the effects of high glucose on the perturbations of renal cell growth.     

Masters or slaves? Vesicle release machinery and the regulation of presynaptic calcium channels

Calcium entry through presynaptic voltage-gated calcium channels is essential for neurotransmitter release. The two major types of presynaptic calcium channels contain a synaptic protein interaction site that physically interacts with synaptic vesicle release proteins. This is thought to tighten the coupling between the sources of calcium entry and the neurotransmitter release machinery. Conversely, the binding of synaptic proteins to presynaptic calcium channels regulates calcium channel activity. Hence, presynaptic calcium channels act not only as the masters of the synaptic release process, but also as key targets for feedback inhibition.     

Calcineurin and intracellular Ca2+-release channels: regulation or association?

The Ca(2+)- and calmodulin-dependent phosphatase calcineurin was reported to interact with the inositol 1,4,5-trisphosphate receptor (IP(3)R) and the ryanodine receptor (RyR) and to modulate their phosphorylation status and activity. However, controversial data on the molecular mechanisms involved and on the functional relevance of calcineurin for these channel-complexes have been described. Hence, we will focus on the functional importance of calcineurin for IP(3)R and RyR function and on the different mechanisms by which Ca(2+)-dependent dephosphorylation can affect the gating of those intracellular Ca(2+)-release channels. Since many studies made use of immunosuppressive drugs that are inhibiting calcineurin activity, we will also have to take the different side effects of these drugs into account for the proper interpretation of the effects of calcineurin on intracellular Ca(2+)-release channels. In addition, it became recently known that various other phosphatases and kinases can associate with these channels, thereby forming macromolecular complexes. The relevance of these enzymes for IP(3)R and RyR functioning will be reviewed since in some cases they could interfere with the effects ascribed to calcineurin. Finally, we will discuss the downstream effects of calcineurin on the regulation of the expression levels of intracellular Ca(2+)-release channels as well as the relation between IP(3)R- and RyR-mediated Ca(2+) release and calcineurin-dependent gene expression.     

Social behavior and comparative genomics: new genes or new gene regulation?

Molecular analyses of social behavior are distinguished by the use of an unusually broad array of animal models. This is advantageous for a number of reasons, including the opportunity for comparative genomic analyses that address fundamental issues in the molecular biology of social behavior. One issue relates to the kinds of changes in genome structure and function that occur to give rise to social behavior. This paper considers one aspect of this issue, whether social evolution involves new genes, new gene regulation, or both. This is accomplished by briefly reviewing findings from studies of the fish Haplochromis burtoni , the vole Microtus ochrogaster , and the honey bee Apis mellifera , with a more detailed and prospective consideration of the honey bee.     

Light Perception in Two Strictly Subterranean Rodents: Life in the Dark or Blue?

Background

The African mole-rats (Bathyergidae, Rodentia) are strictly subterranean, congenitally microphthalmic rodents that are hardly ever exposed to environmental light. Because of the lack of an overt behavioural reaction to light, they have long been considered to be blind. However, recent anatomical studies have suggested retention of basic visual capabilities. In this study, we employed behavioural tests to find out if two mole-rat species are able to discriminate between light and dark, if they are able to discriminate colours and, finally, if the presence of light in burrows provokes plugging behaviour, which is assumed to have a primarily anti-predatory function.

Methodology/Principal Finding

We used a binary choice test to show that the silvery mole-rat Heliophobius argenteocinereus and the giant mole-rat Fukomys mechowii exhibit a clear photoavoidance response to full-spectrum (“white”), blue and green-yellow light, but no significant reaction to ultraviolet or red light during nest building. The mole-rats thus retain dark/light discrimination capabilities and a capacity to perceive short to medium-wavelength light in the photopic range of intensities. These findings further suggest that the mole-rat S opsin has its absorption maximum in the violet/blue part of the spectrum. The assay did not yield conclusive evidence regarding colour discrimination. To test the putative role of vision in bathyergid anti-predatory behaviour, we examined the reaction of mole-rats to the incidence of light in an artificial burrow system. The presence of light in the burrow effectively induced plugging of the illuminated tunnel.

Conclusion/Significance

Our findings suggest that the photopic vision is conserved and that low acuity residual vision plays an important role in predator avoidance and tunnel maintenance in the African mole-rats.