Latest Articles Include:
- Climate crunch year
- Curr Biol 19(14):R537-R539 (2009)
As countries around the world prepare for the crucial climate change conference in December, China tries to boost its green investment, Germany debates the pros and cons of carbon sequestration, the US debate a groundbreaking energy bill, and the UK counts the cost of mitigating climate change in the developing world. Michael Gross reports. - At the frontline
- Curr Biol 19(14):R539-R540 (2009)
Mangroves are at the frontline in the fight against the consequences of climate change. Michael Gross reports. - Lewis C. Cantley
- Curr Biol 19(14):R540-R541 (2009)
- Winter worries
- Curr Biol 19(14):R542 (2009)
- Gibbons
Cunningham C Mootnick A - Curr Biol 19(14):R543-R544 (2009)
- Chromatin: Sub Out the Replacement
Bell O Schübeler D - Curr Biol 19(14):R545-R547 (2009)
Nucleosomes with specific histone variants are incorporated into DNA at sites of transcription and repair. The histone variant H3.3 has been linked to transcriptional regulation, but genetic tests in the fruit fly have yielded surprising results. - Bee Pheromones: Signal or Agent of Manipulation?
Wright GA - Curr Biol 19(14):R547-R548 (2009)
Recent studies have provided a new perspective on the relationship between the honey bee queen and her colony. They suggest that the queen produces a pheromone which pharmacologically manipulates her workers. - Developmental Biology: Pipe's Smoking Guns
Schüpbach T - Curr Biol 19(14):R548-R550 (2009)
The formation of the dorso-ventral body pattern of Drosophila involves the restricted activation of a serine protease cascade in the extracellular space between the egg shell and the embryo. Now, the first molecular links have been identified between ventral gene expression during oogenesis and the activation of the protease cascade in the early embryo. - Cell Division: Righting the Check
Fuller BG Stukenberg PT - Curr Biol 19(14):R550-R553 (2009)
Studies in fission and budding yeast have continuously led the way for analyzing pathways of cell division. Two elegant studies, one from each yeast species, are opening the gates to study one of the final steps of mitosis — silencing the spindle checkpoint. - Innate Immunity: Wounds Burst H2O2 Signals to Leukocytes
Yoo SK Huttenlocher A - Curr Biol 19(14):R553-R555 (2009)
How leukocytes are attracted to wounds is poorly understood. Recent work using zebrafish reveals a novel mechanism of early leukocyte recruitment to wounds through a concentration gradient of hydrogen peroxide. - Genome Dynamics: Transposition and the Single Cell
Finnegan DJ - Curr Biol 19(14):R555-R558 (2009)
Ciliate development requires assembly of functional genes from segments separated by intervening sequences now shown to have properties of transposons. This may be a relic of a time when transposition drove genome evolution, leading to the differentiation of the germline micronucleus and somatic macronucleus. - Limb Development: The Rise and Fall of Retinoic Acid
Lewandoski M Mackem S - Curr Biol 19(14):R558-R561 (2009)
Retinoic acid was thought to play a key instructive role during limb bud initiation and subsequent patterning. New results argue instead that its role is permissive: retinoic acid is essential only to antagonize early axial Fgf signals that otherwise inhibit the limb field. - Four key decades
Williams N - Curr Biol 19(14):R562 (2009)
- Climate and climate change
Ridgwell A Valdes PJ - Curr Biol 19(14):R563-R566 (2009)
- The Continuing Puzzle of the Great Oxidation Event
Sessions AL Doughty DM Welander PV Summons RE Newman DK - Curr Biol 19(14):R567-R574 (2009)
The rise of atmospheric O2 was a milestone in the history of life. Although O2 itself is not a climate-active gas, its appearance would have removed a methane greenhouse present on the early Earth and potentially led to dramatic cooling. Moreover, by fundamentally altering the biogeochemical cycles of C, N, S and Fe, its rise first in the atmosphere and later in the oceans would also have had important indirect effects on Earth's climate. Here, we summarize major lines of evidence from the geological literature that pertain to when and how O2 first appeared in significant amounts in the atmosphere. On the early Earth, atmospheric O2 would initially have been very low, probably <10−5 of the present atmospheric level. Around 2.45 billion years ago, atmospheric O2 rose suddenly in what is now termed the Great Oxidation Event. While the rise of oxygen has been the subject of considerable attention by Earth scientists, several important aspects of this problem remain unre! solved. Our goal in this review is to provide a short summary of the current state of the field, and make the case that future progress towards solving the riddle of oxygen will benefit greatly from the involvement of molecular biologists. - Climate as a Driver of Evolutionary Change
Erwin DH - Curr Biol 19(14):R575-R583 (2009)
The link between biodiversity and climate has been obvious to biologists since the work of von Humboldt in the early 1800s, but establishing the relationship of climate to ecological and evolutionary patterns is more difficult. On evolutionary timescales, climate can affect supply of energy by biotic and abiotic effects. Some of the best evidence for a link between biodiversity and climate comes from latitudinal gradients in diversity, which provide an avenue to explore the more general relationship between climate and evolution. Among the wide range of biotic hypotheses, those with the greatest empirical support indicate that warmer climates have provided the energetic foundation for increased biodiversity by fostering greater population size and thus increased extinction resistance; have increased metabolic scope; have allowed more species to exploit specialized niches as a result of greater available energy; and generated faster speciation and/or lower extinction ra! tes. In combination with geologic evidence for carbon dioxide levels and changing areas of tropical seas, these observations provide the basis for a simple, first-order model of the relationship between climate through the Phanerozoic and evolutionary patterns and diversity. Such a model suggests that we should expect greatest marine diversity during globally warm intervals with dispersed continents, broad shelves and moderately extensive continental seas. Demonstrating a significant evolutionary response to either climate or climatic change is challenging, however, because of continuing uncertainties over patterns of Phanerozoic marine diversity and the variety of factors beyond climate that influence evolution. - Ecological Change, Range Fluctuations and Population Dynamics during the Pleistocene
Hofreiter M Stewart J - Curr Biol 19(14):R584-R594 (2009)
Apart from the current human-induced climate change, the Holocene is notable for its stable climate. In contrast, the preceding age, the Pleistocene, was a time of intensive climatic fluctuations, with temperature changes of up to 15°C occurring within a few decades. These climatic changes have substantially influenced both animal and plant populations. Until recently, the prevailing opinion about the effect of these climatic fluctuations on species in Europe was that populations survived glacial maxima in southern refugia and that populations died out outside these refugia. However, some of the latest studies of modern population genetics, the fossil record and especially ancient DNA reveal a more complex picture. There is now strong evidence for additional local northern refugia for a large number of species, including both plants and animals. Furthermore, population genetic analyses using ancient DNA have shown that genetic diversity and its geographical structure ! changed more often and in more unpredictable ways during the Pleistocene than had been inferred. Taken together, the Pleistocene is now seen as an extremely dynamic era, with rapid and large climatic fluctuations and correspondingly variable ecology. These changes were accompanied by similarly fast and sometimes dramatic changes in population size and extensive gene flow mediated by population movements. Thus, the Pleistocene is an excellent model case for the effects of rapid climate change, as we experience at the moment, on the ecology of plants and animals. - Climate Disruption and Biodiversity
Pimm SL - Curr Biol 19(14):R595-R601 (2009)
'Global warming' may be a familiar term, but it is seriously misleading. Human actions are causing a massive disruption to the planet's climate that is severe, rapid, very variable over space and time, and highly complex. The biosphere itself is complex and its responses to even simple changes are difficult to predict in detail. One can likely only be certain that many changes will be unexpected and some unfortunate. Even the simple, slow warming of the climate will produce complex consequences to species numbers and distributions because of how species depend on each other. An alternative approach to worrying about details is to concentrate on understanding the most significant ecological changes, ones that are irreversible — so-called 'tipping points'. Once such a point has been passed, even if society managed to restore historical climatic conditions, it might not restore the historical ecological patterns. Nowhere is this more obvious than in the loss of ! species, for we cannot recreate them. Climate disruptions may cause the loss of a large fraction of the planet's biodiversity, even if the only mechanism were to be species ranges moving uphill as temperatures rise. - Impacts of Climate Change on Marine Organisms and Ecosystems
Brierley AS Kingsford MJ - Curr Biol 19(14):R602-R614 (2009)
Human activities are releasing gigatonnes of carbon to the Earth's atmosphere annually. Direct consequences of cumulative post-industrial emissions include increasing global temperature, perturbed regional weather patterns, rising sea levels, acidifying oceans, changed nutrient loads and altered ocean circulation. These and other physical consequences are affecting marine biological processes from genes to ecosystems, over scales from rock pools to ocean basins, impacting ecosystem services and threatening human food security. The rates of physical change are unprecedented in some cases. Biological change is likely to be commensurately quick, although the resistance and resilience of organisms and ecosystems is highly variable. Biological changes founded in physiological response manifest as species range-changes, invasions and extinctions, and ecosystem regime shifts. Given the essential roles that oceans play in planetary function and provision of human sustenance, t! he grand challenge is to intervene before more tipping points are passed and marine ecosystems follow less-buffered terrestrial systems further down a spiral of decline. Although ocean bioengineering may alleviate change, this is not without risk. The principal brake to climate change remains reduced CO2 emissions that marine scientists and custodians of the marine environment can lobby for and contribute to. This review describes present-day climate change, setting it in context with historical change, considers consequences of climate change for marine biological processes now and in to the future, and discusses contributions that marine systems could play in mitigating the impacts of global climate change. - Biological Approaches to Global Environment Change Mitigation and Remediation
Woodward FI Bardgett RD Raven JA Hetherington AM - Curr Biol 19(14):R615-R623 (2009)
One of the most pressing and globally recognized challenges is how to mitigate the effects of global environment change brought about by increasing emissions of greenhouse gases, especially CO2. In this review we evaluate the potential contribution of four biological approaches to mitigating global environment change: reducing atmospheric CO2 concentrations through soil carbon sequestration and afforestation; reducing predicted increases in global surface temperatures through increasing the albedo of crop plants; and fertilizing the oceans to increase primary productivity and CO2 drawdown. We conclude that none of these biological approaches are 'magic bullets' capable of reversing environmental changes brought about by increasing emissions of greenhouse gases. However, it is possible that increasing crop albedo and soil carbon sequestration might contribute towards mitigation on a regional scale. In the absence of legally binding international agreements to reduce! CO2 emissions, we propose that: increased efforts are made to identify novel biological mitigatory strategies; further research is conducted to minimise the uncertainties present in all four of the biological approaches described; and pilot-level field work is conducted to examine the feasibility of the most promising strategies. Finally, it is essential to engage with the public concerning strategies for mitigating the effects of climate change because the majority of the biological approaches have effects, quite possibly of a negative nature, on ecosystem services and land usage. - EEG Responses to Visual Landmarks in Flying Pigeons
Vyssotski AL Dell'Omo G Dell'Ariccia G Abramchuk AN Serkov AN Latanov AV Loizzo A Wolfer DP Lipp HP - Curr Biol 19(14):1159-1166 (2009)
Background GPS analysis of flight trajectories of pigeons can reveal that topographic features influence their flight paths. Recording electrical brain activity that reflects attentional processing could indicate objects of interest that do not cause changes in the flight path. Therefore, we investigated whether crossing particular visual landmarks when homing from a familiar release site is associated with changes in EEG. Results Birds carried both data-loggers for recording GPS position and EEG during flight. First, we classified characteristic EEG frequencies of caged birds and found five main bands: A: 0–3, B: 3–12, C: 12–60, D: 60–130, and E: 130–200 Hz. We analyzed changes in these activity bands when pigeons were released over sea (a featureless environment) and over land. Passing over the coastline and other prominent landmarks produced a pattern of EEG alterations consisting of two phases: activation of EEG in the high-frequency bands (D and/or E), followed by activation of C. Overlaying the EEG activity with GPS tracks allowed us to identify topographical features of interest for the pigeons that were not recognizable by distinct changes of their flight path. Conclusions We provide evidence that EEG analysis can identify landmarks and objects of interest during homing. Middle-frequency activity (C) reflects visual perception of prominent landmarks, whereas activation of higher frequencies (D and E) is linked with information processing at a higher level. Activation of E bands is likely to reflect an initial process of orientation and is not necessarily linked with processing of visual information. - Cellular Dissection of Circadian Peptide Signals with Genetically Encoded Membrane-Tethered Ligands
Choi C Fortin JP McCarthy E Oksman L Kopin AS Nitabach MN - Curr Biol 19(14):1167-1175 (2009)
Background Neuropeptides regulate many biological processes. Elucidation of neuropeptide function requires identifying the cells that respond to neuropeptide signals and determining the molecular, cellular, physiological, and behavioral consequences of activation of their cognate G protein-coupled receptors (GPCRs) in those cells. As a novel tool for addressing such issues, we have developed genetically encoded neuropeptides covalently tethered to a glycosylphosphatidylinositol (GPI) glycolipid anchor on the plasma membrane ("t-peptides"). Results t-peptides cell-autonomously induce activation of their cognate GPCRs in cells that express both the t-peptide and its receptor. In the neural circuit controlling circadian rest-activity rhythms in Drosophila melanogaster, rhythmic secretion of the neuropeptide pigment-dispersing factor (PDF) and activation of its GPCR (PDFR) are important for intercellular communication of phase information and coordination of clock neuron oscillation. Broad expression of t-PDF in the circadian control circuit overcomes arrhythmicity induced by pdf01 null mutation, most likely as a result of activation of PDFR in PDFR-expressing clock neurons that do not themselves secrete PDF. More restricted expression of t-PDF suggests that activation of PDFR accelerates cellular timekeeping in some clock neurons while decelerating others. Conclusions The activation of PDFR in pdf01 null mutant flies—which lack PDF-mediated intercellular transfer of phase information—induces strong rhythmicity in constant darkness, thus establishing a distinct role for PDF signaling in the circadian control circuit independent of the intercellular communication of temporal phase information. The t-peptide technology should provide a useful tool for cellular dissection of bioactive peptide signaling in a variety of organisms and physiological contexts. - A Novel Protein Phosphatase 1-Dependent Spindle Checkpoint Silencing Mechanism
Vanoosthuyse V Hardwick KG - Curr Biol 19(14):1176-1181 (2009)
The spindle checkpoint is a surveillance system acting in mitosis to delay anaphase onset until all chromosomes are properly attached to the mitotic spindle [1] and [2]. When the checkpoint is activated, the Mad2 and Mad3 proteins directly bind and inhibit Cdc20, which is an essential activator of an E3 ubiquitin ligase known as the anaphase-promoting complex (APC) [3]. When the checkpoint is satisfied, Cdc20-APC is activated and polyubiquitinates securin and cyclin, leading to the dissolution of sister chromatid cohesion and mitotic progression. Several protein kinases play critical roles in spindle checkpoint signaling, but the mechanism (or mechanisms) by which they inhibit mitotic progression remains unclear [4]. Furthermore, it is not known whether their activity needs to be reversed by protein phosphatases before anaphase onset can occur. Here we employ fission yeast to show that Aurora (Ark1) kinase activity is directly required to maintain spindle checkpoint ar! rest, even in the presence of many unattached kinetochores. Upon Ark1 inhibition, checkpoint complexes are disassembled and cyclin B is rapidly degraded. Importantly, checkpoint silencing and cyclin B degradation require the kinetochore-localized isoform of protein phosphatase 1 (PP1Dis2). We propose that PP1Dis2-mediated dephosphorylation of checkpoint components forms a novel spindle checkpoint silencing mechanism. - Protein Phosphatase 1 Regulates Exit from the Spindle Checkpoint in Budding Yeast
Pinsky BA Nelson CR Biggins S - Curr Biol 19(14):1182-1187 (2009)
Accurate chromosome segregation depends on sister kinetochores coming under tension when they make bioriented attachments to microtubules from opposite poles. The spindle checkpoint halts the cell cycle in response to defects in generating proper attachments or tension on kinetochores [1] and [2], although the precise signal that triggers the checkpoint is unclear because tension and attachment are coupled [3]. The target of the checkpoint is the Cdc20 protein, which initiates the anaphase-promoting complex (APC)-dependent degradation of the anaphase inhibitor Pds1/securin [4]. Although the molecular details of spindle checkpoint activation are still being elucidated, phosphorylation by at least four kinases is a crucial requirement [5]. However, less is known about the mechanisms that silence the checkpoint after kinetochores biorient. Here, we show that the catalytic subunit of the budding yeast protein phosphatase 1 (PP1) homolog, Glc7, regulates exit from the check! point. Glc7 overexpression prevents spindle checkpoint activation in response to both tension and attachment defects. Although glc7 mutant cells are able to efficiently release from a non-checkpoint-mediated metaphase arrest, they are uniquely sensitive to transient spindle checkpoint activation as a result of a failure in spindle checkpoint exit. We therefore propose that PP1 activity silences the checkpoint by reversing key phosphorylation events. - Gibberellin Signaling Controls Cell Proliferation Rate in Arabidopsis
Achard P Gusti A Cheminant S Alioua M Dhondt S Coppens F Beemster GT Genschik P - Curr Biol 19(14):1188-1193 (2009)
Plant growth involves the integration of many environmental and endogenous signals that together with the intrinsic genetic program determine plant size. At the cellular level, growth rate is regulated by the combined activity of two processes: cell proliferation and expansion. Gibberellins (GA) are plant-specific hormones that play a central role in the regulation of growth and development with respect to environmental variability [1], [2] and [3]. It is well established that GA promote growth through cell expansion by stimulating the destruction of growth-repressing DELLA proteins (DELLAs) [1], [4], [5] and [6]; however, their effects on cell proliferation remain unknown. Kinematic analysis of leaf and root meristem growth revealed a novel function of DELLAs in restraining cell production. Moreover, by visualizing the cell cycle marker cyclinB1::β-glucuronidase in GA-signaling mutants, we show that GA modulate cell cycle activity in the root meristem via a DELLA-dep! endent mechanism. Accordingly, expressing gai (a nondegradable DELLA protein [4]) solely in root meristem reduced substantially the number of dividing cells. We also show that DELLAs restrain cell production by enhancing the levels of the cell cycle inhibitors Kip-related protein 2 (KRP2) and SIAMESE (SIM). Therefore, DELLAs exert a general plant growth inhibitory activity by reducing both cell proliferation and expansion rates, enabling phenotypic plasticity. - Gibberellin Signaling in the Endodermis Controls Arabidopsis Root Meristem Size
Ubeda-Tomás S Federici F Casimiro I Beemster GT Bhalerao R Swarup R Doerner P Haseloff J Bennett MJ - Curr Biol 19(14):1194-1199 (2009)
Plant growth is driven by cell proliferation and elongation [1]. The hormone gibberellin (GA) regulates Arabidopsis root growth [2], [3], [4] and [5] by controlling cell elongation [6], but it is currently unknown whether GA also controls root cell proliferation. Here we show that GA biosynthetic mutants are unable to increase their cell production rate and meristem size after germination. GA signals the degradation of the DELLA growth repressor proteins [7], [8], [9], [10], [11] and [12] GAI and RGA, promoting root cell production. Targeting the expression of gai (a non-GA-degradable mutant form of GAI) in the root meristem disrupts cell proliferation. Moreover, expressing gai in dividing endodermal cells was sufficient to block root meristem enlargement. We report a novel function for GA regulating cell proliferation where this signal acts by removing DELLA in a subset of, rather than all, meristem cells. We suggest that the GA-regulated rate of expansion of dividing! endodermal cells dictates the equivalent rate in other root tissues. Cells must double in size prior to dividing but cannot do so independently, because they are physically restrained by adjacent tissues with which they share cell walls. Our study highlights the importance of probing regulatory mechanisms linking molecular- and cellular-scale processes with tissue and organ growth responses. - Sulfation of Eggshell Components by Pipe Defines Dorsal-Ventral Polarity in the DrosophilaEmbryo
Zhang Z Stevens LM Stein D - Curr Biol 19(14):1200-1205 (2009)
Drosophila embryonic dorsal-ventral (DV) polarity is controlled by a group of sequentially acting serine proteases located in the fluid-filled perivitelline space between the embryonic membrane and the eggshell, which generate the ligand for the Toll receptor on the ventral side of the embryo [1], [2] and [3]. Spatial control of the protease cascade relies on the Pipe sulfotransferase, a fly homolog of vertebrate glycosaminoglycan-modifying enzymes [4], [5] and [6], which is expressed in ventral cells of the follicular epithelium surrounding the developing oocyte. Here we show that the vitelline membrane-like (VML) protein [7] undergoes Pipe-dependent sulfation and, consistent with a role in conveying positional information from the egg chamber to the embryo, becomes incorporated into the eggshell at a position corresponding to the location of the follicle cells from which it was secreted. Although VML influences embryonic DV pattern in a sensitized genetic background,! VML is not essential for DV axis formation, suggesting that there is redundancy in the composition of the Pipe enzymatic target. Correspondingly, we find that additional structural components of the vitelline membrane undergo Pipe-dependent sulfation. In identifying the elusive targets of Pipe, this work points to the vitelline membrane as the source of signals that generate the Drosophila DV axis. - Dopamine Receptor Activation By Honey Bee Queen Pheromone
Beggs KT Mercer AR - Curr Biol 19(14):1206-1209 (2009)
Queen mandibular pheromone (QMP) is produced by honey bee queens and used to regulate the behavior and physiology of their nestmates [1]. QMP has recently been shown to block aversive learning in young worker bees, an effect that can be mimicked by treating bees with one of QMP's key components, homovanillyl alcohol (HVA) [2]. Although the mechanisms underlying this blockade remain unclear, HVA has been found to lower brain dopamine levels and to alter intracellular levels of cAMP in brain centers involved in learning and memory [3]. These findings led to the hypothesis that HVA targets dopamine pathways in the brain [3], which are known to play a critical role in the formation of aversive olfactory memories [4], [5], [6], [7] and [8]. Here, we investigate the possibility that HVA interacts directly with dopamine receptors in the bee. We show that HVA selectively activates the D2-like dopamine receptor AmDOP3 but has neither agonist nor antagonist activity on the D1-li! ke receptors AmDOP1 or AmDOP2 nor agonist activity on the octopamine receptor AmOA1. These results suggest a direct molecular mechanism by which queen pheromone can modulate dopamine signaling pathways. They also implicate the dopamine receptor AmDOP3 in HVA-induced blockade of aversive learning in young worker bees. - Spindle Assembly in the Absence of a RanGTP Gradient Requires Localized CPC Activity
Maresca TJ Groen AC Gatlin JC Ohi R Mitchison TJ Salmon ED - Curr Biol 19(14):1210-1215 (2009)
During animal cell division, a gradient of GTP-bound Ran is generated around mitotic chromatin [1] and [2]. It is generally accepted that this RanGTP gradient is essential for organizing the spindle, because it locally activates critical spindle assembly factors [3], [4] and [5]. Here, we show in Xenopus laevis egg extract, where the gradient is best characterized, that spindles can assemble in the absence of a RanGTP gradient. Gradient-free spindle assembly occurred around sperm nuclei but not around chromatin-coated beads and required the chromosomal passenger complex (CPC). Artificial enrichment of CPC activity within hybrid bead arrays containing both immobilized chromatin and the CPC supported local microtubule assembly even in the absence of a RanGTP gradient. We conclude that RanGTP and the CPC constitute the two major molecular signals that spatially promote microtubule polymerization around chromatin. Furthermore, we hypothesize that the two signals mainly ori! ginate from discreet physical sites on the chromosomes to localize microtubule assembly around chromatin: a RanGTP signal from any chromatin and a CPC-dependent signal predominantly generated from centromeric chromatin. - Synergism of Red and Blue Light in the Control of Arabidopsis Gene Expression and Development
Sellaro R Hoecker U Yanovsky M Chory J Casal JJ - Curr Biol 19(14):1216-1220 (2009)
The synergism between red and blue light in the control of plant growth and development [1] and [2] requires the coaction of the red light photoreceptor phytochrome B (phyB) and the blue light and UV-A receptor cryptochromes (cry) [3]. Here, we describe the mechanism of the coaction of these photoreceptors in controlling both development and physiology. In seedlings grown under red light, a transient supplement with blue light induced persistent changes in the transcriptome and growth patterns. Blue light enhanced the expression of the transcription factors LONG HYPOCOTYL 5 (HY5) and HOMOLOG OF HY5 (HYH) [4] and of SUPPRESSOR OF PHYA 1 (SPA1) and SPA4[5]. HY5 and HYH enhanced phyB signaling output beyond the duration of the blue light signal, and, contrary to their known role as repressors of phyA signaling [5], SPA1 and SPA4 also enhanced phyB signaling. These observations demonstrate that the mechanism of synergism involves the promotion by cry of positive regulators! of phyB signaling. The persistence of the light-derived signal into the night commits the seedling to a morphogenetic and physiological program consistent with a photosynthetic lifestyle. - Transcription in the Absence of Histone H3.3
Hödl M Basler K - Curr Biol 19(14):1221-1226 (2009)
Di- and trimethylation of histone H3 lysine 4 (H3K4me2 and H3K4me3) are hallmarks of chromatin at active genes [1]. The major fraction of K4-methylated histone H3 is the variant H3 (termed H3.3 in Drosophila) [2], which replaces canonical H3 (H3.2) in transcribed genes [3] and [4]. Here, we genetically address the in vivo significance of such K4 methylation by replacing wild-type H3.3 with a mutant form (H3.3K4A) that cannot be methylated. We monitored the transcription that occurs in response to multiple well-described signaling pathways. Surprisingly, the transcriptional outputs of these pathways remain intact in H3.3K4A mutant cells. Even the complete absence of both H3.3 genes does not noticeably affect viability or function of cells: double mutant animals are viable but sterile. Fertility can be rescued by K4-containing versions of H3.3, but not with mutant H3.3 (H3.3K4A) or with canonical H3.2. Together, these data suggest that in Drosophila, presence of H3.3K4me! in the chromatin of active genes is dispensable for successful transcription in most cells and only plays an important role in reproductive tissues. - RAN GTPase Is a RASSF1A Effector Involved in Controlling Microtubule Organization
Dallol A Hesson LB Matallanas D Cooper WN O'Neill E Maher ER Kolch W Latif F - Curr Biol 19(14):1227-1232 (2009)
RASSF1A is a tumor suppressor gene that is inactivated by hypermethylation of its promoter region in most types of human cancers [1], [2] and [3]. The incidence of spontaneous or induced tumors is significantly higher in Rassf1a−/− mice than in wild-type mice, confirming the tumor suppressor function of RASSF1A [4] and [5]. RASSF1A promotes apoptosis mainly through its interaction with the proapoptotic serine/threonine STE20-like kinases MST1 and 2 [6] and [7]. However, Rassf1a−/− mice do not show overt signs of deregulated apoptosis [4] and [5], suggesting that other RASSF1A effectors are also critical for tumor suppression. In a proteomics screen, we identified RAN GTPase, MST1 and 2 kinases, and α- and γ-tubulin as RASSF1A-interacting proteins. We show that RASSF1A-induced microtubule hyperstability, a hallmark of RASSF1A expression [8] and [9], is RAN-GTP dependent. RASSF1A promotes the accumulation of the GTP-bound form of RAN via the MST2-induced phosph! orylation of RCC1. Depletion of RASSF1A results in mislocalization of RCC1 to the mitotic spindle and spindle poles, leading to mitotic spindle abnormalities and prometaphase block. A similar mitotic delay is also observed with MST2 depletion. These findings reveal a mechanism for how RASSF1A controls microtubule stability and for how its loss compromises the integrity of the mitotic spindle, leading to aneuploidy and tumorigenesis. - C. Elegans Are Protected from Lethal Hypoxia by an Embryonic Diapause
Miller DL Roth MB - Curr Biol 19(14):1233-1237 (2009)
At least 100 mammalian species exhibit embryonic diapause, where fertilized embryos arrest development in utero until suitable seasonal or nutritional environments are encountered [1] and [2]. Delaying maternal investments in producing offspring allows these animals to utilize limited resources to survive while searching for better conditions and ensures that progeny are not produced when they are unlikely to survive. In addition, embryos may be protected from external environmental vicissitudes while in utero [3]. Here we demonstrate embryonic diapause in C. elegans, and show that this diapause protects embryos from otherwise lethal hypoxia. Diapausing embryos in utero require san-1 to survive, indicating that hypoxia-induced embryonic diapause may be mechanistically related to suspended animation. Furthermore, we show that neuronal HIF-1 activity in the adult dictates the O2 tension at which embryonic diapause is engaged. We suggest that the maternal perception of hy! poxia stimulates a response to protect embryos in utero by inducing diapause, a natural form of suspended animation. This response is likely to be an important strategy to improve offspring survival in harsh conditions and allow adults to find environments more suitable for reproductive success. - ASQ2 Encodes a TBCC-like Protein Required for Mother-Daughter Centriole Linkage and Mitotic Spindle Orientation
Feldman JL Marshall WF - Curr Biol 19(14):1238-1243 (2009)
An intriguing feature of centrioles is that these highly complicated microtubule-based structures duplicate once per cell cycle, affording the cell precise control over their number. Each cell contains exactly two centrioles, linked together as a pair, one of which is a mother centriole formed in a previous cell cycle and the other of which is a daughter centriole whose assembly is templated by the mother. Neither the molecular basis nor the functional role of mother-daughter centriole linkage is understood. We have identified a mutant, asq2, with defects in centriole linkage. asq2 mutant cells have variable numbers of centrioles and centriole positioning defects. Here, we show that ASQ2 encodes the conserved protein Tbccd1, a member of a protein family including a tubulin folding cochaperone and the retinitis pigmentosa protein RP2, involved in tubulin quality control during ciliogenesis. We characterize mitosis in asq2 cells and show that the majority of cells establ! ish a bipolar spindle but have defects in spindle orientation. Few asq2 cells have centrioles at both poles, and these cells have properly positioned spindles, indicating that centrioles at the poles might be important for spindle orientation. The defects in centriole number control, centriole positioning, and spindle orientation appear to arise from perturbation of centriole linkage mediated by Tbccd1/Asq2p.
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