Corruption of host seven-transmembrane proteins by pathogenic microbes: a common theme in animals and plants?

Human diseases like AIDS, malaria, and pneumonia are caused by pathogens that corrupt host chemokine G-protein coupled receptors for molecular docking. Comparatively, little is known about plant host factors that are required for pathogenesis and that may serve as receptors for the entry of pathogenic microbes. Here, we review potential analogies between human chemokine receptors and the plant seven-transmembrane MLO protein, a candidate serving a dual role as docking molecule and defence modulator for the phytopathogenic powdery mildew fungus.     

Several steps of lateral gene transfer followed by events of ‘birth-and-death’ evolution shaped a fungal sorbicillinoid biosynthetic gene cluster

Dung beetles (subfamily Scarabaeinae) are popular model organisms in ecology and developmental biology, and for the last two decades they have experienced a systematics renaissance with the adoption of modern phylogenetic approaches. Within this period 16 key phylogenies and numerous additional studies with limited scope have been published, but higher-level relationships of this pivotal group of beetles remain contentious and current classifications contain many unnatural groupings. The present study provides a robust phylogenetic framework and a revised classification of dung beetles. We assembled the so far largest molecular dataset for dung beetles using sequences of 8 gene regions and 547 terminals including the outgroup taxa. This dataset was analyzed using Bayesian, maximum likelihood and parsimony approaches. In order to test the sensitivity of results to different analytical treatments, we evaluated alternative partitioning schemes based on secondary structure, domains and codon position. We assessed substitution models adequacy using Bayesian framework and used these results to exclude partitions where substitution models did not adequately depict the processes that generated the data. We show that exclusion of partitions that failed the model adequacy evaluation has a potential to improve phylogenetic inference, but efficient implementation of this approach on large datasets is problematic and awaits development of new computationally advanced software. In the class Insecta it is uncommon for the results of molecular phylogenetic analysis to lead to substantial changes in classification. However, the results presented here are congruent with recent morphological studies and support the largest change in dung beetle systematics for the last 50 years. Here we propose the revision of the concepts for the tribes Deltochilini (Canthonini), Dichotomiini and Coprini; additionally, we redefine the tribe Sisyphini. We provide and illustrate synapomorphies and diagnostic characters supporting the new concepts to facilitate diagnosability of the redefined tribes. As a result of the proposed changes a large number of genera previously assigned to these tribes are now left outside the redefined tribes and are treated as incertae sedis. The present study redefines dung beetles classification and gives new insight into their phylogeny. It has broad implications for the systematics as well as for various ecological and evolutionary analyses in dung beetles.     

Canonical and non-canonical autophagy: variations on a common theme of self-eating?

The autophagosome is the central organelle in macroautophagy, a vacuolar lysosomal catabolic pathway that degrades cytoplasmic material to fuel starving cells and eliminates intracellular pathogens. Macroautophagy has important physiological roles during development, ageing and the immune response, and its cytoprotective function is compromised in various diseases. A set of autophagy-related (ATG) proteins is hierarchically recruited to the phagophore, the initial membrane template in the construction of the autophagosome. However, recent findings suggest that macroautophagy can also occur in the absence of some of these key autophagy proteins, through the unconventional biogenesis of canonical autophagosomes. Such alternatives to the evolutionarily conserved scheme might provide additional therapeutic opportunities.     

Opinion: Cell entry machines: a common theme in nature?

Molecular machines orchestrate the translocation and entry of pathogens through host cell membranes, in addition to the uptake and release of molecules during endocytosis and exocytosis. Viral cell entry requires a family of glycoproteins, and the structural organization and function of these viral glycoproteins are similar to the SNARE proteins, which are known to be involved in intracellular vesicle fusion, endocytosis and exocytosis. Here, we propose that a family of bacterial membrane proteins that are responsible for cell-mediated adherence and entry resembles the structural architecture of both viral fusion proteins and eukaryotic SNAREs and might therefore share similar, but distinct, mechanisms of cell membrane translocation. Furthermore, we propose that the recurrence of these molecular machines across species indicates that these architectural motifs were evolutionarily selected because they provided the best solution to ensure the survival of pathogens within a particular environment.     

Photosynthetic reaction centres: variations on a common structural theme?

From their hybrid properties, the reaction centres of green sulphur bacteria and heliobacteria seem to be the missing links between the two branches of the reaction centre family, typified by higher plant photosystem I and the purple bacterial reaction centre. This suggests that all of the diverse types of photosynthetic reaction centres have closer structural resemblances than was previously thought.     

Making more microtubules by severing: a common theme of noncentrosomal microtubule arrays?

Two related enzymes, katanin and spastin, use the energy from ATP hydrolysis to sever microtubules. Two new studies (one in this issue; see McNally et al., p. 881) show that microtubule severing by katanin provides a means for increasing microtubule density in meiotic spindles. Interestingly, loss of spastin leads to a sparser microtubule array in axons and synaptic boutons. Together, these studies hint at a wider role for microtubule-severing enzymes in the formation and organization of noncentrosomal microtubule arrays by generating new seeds for microtubule growth.     

Function of the phosphatidylinositol transfer protein gene family: is phosphatidylinositol transfer the mechanism of action?

Phosphatidylinositol transfer proteins (PITPs) bind and facilitate the transport of phosphatidylinositol (PI) and phosphatidylcholine between membrane compartments. They are highly conserved proteins, are found in both unicellular and multicellular organisms, and can be present as a single domain or as part of a larger, multi-domain protein. The hallmark of PITP proteins is their ability to sequester PI in their hydrophobic pocket. Ablation or knockdown of specific isoforms in vivo has wide ranging effects such as defects in signal transduction via phospholipase C and phosphoinositide 3-kinase, membrane trafficking, stem cell viability, Drosophila phototransduction, neurite outgrowth, and cytokinesis. In this review, we identify the common mechanism underlying each of these phenotypes as the cooperation between PITP proteins and lipid kinases through the provision of PI for phosphorylation. We propose that recruitment and concentration of PITP proteins at specific membrane sites are required for PITP proteins to execute their function rather than lipid transfer.     

The GTP-binding domain of McrB: more than just a variation on a common theme?

The methylation-dependent restriction endonuclease McrBC from Escherichia coli K12 cleaves DNA containing two R(m)C dinucleotides separated by about 40 to 2000 base-pairs. McrBC is unique in that cleavage is totally dependent on GTP hydrolysis. McrB is the GTP binding and hydrolyzing subunit, whereas MrC stimulates its GTP hydrolysis. The C-terminal part of McrB contains the sequences characteristic for GTP-binding proteins, consisting of the GxxxxGK(S/T) motif (position 201-208), followed by the DxxG motif (position 300-303). The third motif (NKxD) is present only in a non-canonical form (NTAD 333-336). Here we report a mutational analysis of the putative GTP-binding domain of McrB. Amino acid substitutions were initially performed in the three proposed GTP-binding motifs. Whereas substitutions in motif 1 (P203V) and 2 (D300N) show the expected, albeit modest effects, mutation in the motif 3 is at variance with the expectations. Unlike the corresponding EF-Tu and ras -p21 variants, the D336N mutation in McrB does not change the nucleotide specificity from GTP to XTP, but results in a lack of GTPase stimulation by McrC. The finding that McrB is not a typical G protein motivated us to perform a search for similar sequences in DNA databases. Eight microbial sequences were found, mainly from unfinished sequencing projects, with highly conserved sequence blocks within a presumptive GTP-binding domain. From the five sequences showing the highest homology, 17 invariant charged or polar residues outside the classical three GTP-binding motifs were identified and subsequently exchanged to alanine. Several mutations specifically affect GTP affinity and/or GTPase activity. Our data allow us to conclude that McrB is not a typical member of the superfamily of GTP-binding proteins, but defines a new subfamily within the superfamily of GTP-binding proteins, together with similar prokaryotic proteins of as yet unidentified function.     

Degradation of negative regulators: a common theme in hormone and light signaling networks?

Signal transduction pathways often modulate both positively and negatively acting components to optimize the efficiency of a signal. Recent results have shown that plants make extensive use of regulated proteolysis to modulate signal transduction pathways. An emerging theme from hormone (e.g. auxin and gibberellin) and light signaling pathways is signal or stimulus-induced degradation of negative regulators to optimize plant growth and development.     

Aurora kinases and spindle assembly: Variations on a common theme?

The Aurora A (AurA) serine/threonine kinase controls multiple aspects of cell division and plays a key role in centrosome maturation and bipolar spindle assembly. The pleiotropic functions of AurA depend on its interaction with several cofactors, the best known of which is TPX2. TPX2 targets AurA to spindle microtubules (MTs) and activates it, both allosterically and by protecting the activation loop (T-loop) of the kinase domain from dephosphorylation. Although several factors have been implicated in the regulation of AurA at centrosomes, the underlying mechanism has remained elusive, and the existence of a distinct centrosome-specific AurA activator has been proposed. Our recent study has identified this activator as Cep192/Spd-2, one of the key factors in centrosome biogenesis. Cep192 targets AurA to centrosomes, where it promotes its activation by a novel, oligomerization-dependent mechanism characterized by extensive T-loop phosphorylation and high kinase activity. This process is key to the function of centrosomes as microtubule-organizing centers. Here, our findings are discussed in the context of other recent studies on the Aurora kinases, with an emphasis on their role in spindle assembly. The collected evidence suggests that the ‘hot spots’ of MT nucleation, centrosomes and kinetochores, rely on the oligomerization-mediated mechanism of activation of AurA and AurB, respectively.     

What is the significance of the arbuscular mycorrhizal colonisation of many economically important crop plants?

Arbuscular mycorrhizal (AM) symbioses are widespread in land plants but the extent to which they are functionally important in agriculture remains unclear, despite much previous research. We ask focused questions designed to give new perspectives on AM function, some based on recent research that is overturning past beliefs. We address factors that determine growth responses (from positive to negative) in AM plants, the extent to which AM plants that lack positive responses benefit in terms of nutrient (particularly phosphate: P) uptake, whether or not AM and nonmycorrhizal (NM) plants acquire different forms of soil P, and the cause(s) of AM ??growth depressions??. We consider the relevance of laboratory work to the agricultural context, including effects of high (available) soil P on AM fungal colonisation and whether AM colonisation may be deleterious to crop production due to fungal ??parasitism??. We emphasise the imperative for research that is aimed at increasing benefits of AM symbioses in the field at a time of increasing prices of P-fertiliser, and increasing demands on agriculture to feed the world. In other words, AM symbioses have key roles in providing ecosystem services that are receiving increasing attention worldwide.     

If everything is everywhere, do they share a common gene pool?

Marine phytoplanktons are highly dispersed with large population sizes and are often considered to be homogenous over their entire range. Thus, using this definition, one would predict that everything is everywhere for these microbes. However, recent molecular analyses have shown both spatial and temporal compartmentalisation in phytoplankton communities, thus calling into question the idea that everything is everywhere, especially if they do not share a global gene pool. Examples are present to document the range of biogeography that has been reported in the phytoplankton and a hypothesis as to how this relates to species evolution on a geological time scale is provided.     

Preventing retinal apoptosis — Is there a common therapeutic theme?

There is an urgent need for therapies for retinal diseases; retinitis pigmentosa sufferers have no treatment options available and those targeted at other retinopathies have shown limited effectiveness. The process of programmed cell death or apoptosis although complex, remains a possible target for the treatment of retinal diseases. Having identified apoptosis in the vertebrate retina in populations of immature neurons as an essential part of development it was proposed that re-activation of these developmental cell death pathways might provide insight into the death mechanisms operating in retinal diseases. However, the discovery that numerous factors initiate and mediate the apoptotic cascade in mature photoreceptors has resulted in a relatively untargeted approach to examining and arresting apoptosis in the retina. In the last 5 years, mouse models have been treated with a diverse range of drugs or factors including anti-oxidants, growth factors, steroid hormones, calcium/calpain inhibitors and tetracycline antibiotics. Therefore to draw a unifying theme from these broad research areas is challenging. However, this review focusses on two targets which are currently under investigation, reactive oxygen species and mammalian target of rapamycin, drawing together the common themes of these research areas.     

Reappraising the theme of breeding systems in Echinococcus: is outcrossing a rare phenomenon?

Selfing has been considered the most common mode of reproduction in Echinococcus flatworms. However, population genetic studies on the asexual larval stage involving nuclear co-dominant markers have not always revealed significant heterozygote deficiencies--the expected outcome of a regularly and highly inbred population. In this study, we analysed the genetic structure of Echinococcus granulosus sensu lato populations from Southern Brazil during their adult (sexual) stage using 1 mitochondrial and 1 nuclear marker (cox 1 and mdh, respectively). We show that parasite genetic differentiation is largest among definitive hosts (domestic dogs) from different farms, suggesting that transmission is mostly maintained within a farm. Moreover, we show that heterozygote deficiencies are not significant, and we suggest that outbreeding is the most common mode of reproduction of the parasite in that region.     

Intracellular accommodation of microbes by plants: a common developmental program for symbiosis and disease?

Plant cells engage in mutualistic and parasitic endosymbioses with a wide variety of microorganisms, ranging from Gram-negative (Rhizobium, Nostoc) and Gram-positive bacteria (Frankia), to oomycetes (Phytophthora), Chytridiomycetes, Zygomycetes (arbuscular mycorrhizal fungi) and true fungi (Erysiphe, ascomycete; Puccinia, basidiomycete). Endosymbiosis is characterised by the 'symbiosome', a compartment within host cells in which the symbiotic microorganism is either partially or completely enclosed by a host-derived membrane. The analysis of plant mutants indicates that the genetic requirements for the interaction with rhizobia and arbuscular mycorrhiza fungi are partially overlapping. The extent to which plants use similar or identical developmental programs for the intracellular accommodation of different microorganisms is, however, not clear. For example, plant cells actively weaken their cell wall to facilitate bacterial colonisation, whereas penetration by fungal symbionts appears not to be assisted in this manner. Moreover, different transport requirements are imposed on the symbiotic interface of different interactions indicating that additional system-specific components are likely to exist.     

Hamsters running on time: is the lateral habenula a part of the clock?

Previous anatomical and physiological studies have implicated the lateral habenula, and especially its medial division (LHbM), as a candidate component of the circadian timing system in rodents. We assayed lateral habenula rhythmicity in rodents using c-FOS immunohistochemistry and found a robust rhythm in immunoreactive cell counts in the LHbM, with higher counts during the dark phase of a light-dark (LD) cycle and during subjective night in constant darkness. We have also observed an obvious asymmetry of c-FOS expression in the LHbM of behaviorally "split" hamsters in constant light, but only during their active phase (when they were running in wheels). Locomotor activity rhythms appear to be regulated by the suprachiasmatic nucleus (SCN) via multiple output pathways, one of which might be diffusible while the other might be neural, involving the lateral habenula.