CD95: more than just a death factor?

The CD95 protein delivers crucial signals for lymphocyte death, and may also negatively regulate T-lymphocyte activation by preventing the influx of calcium ions from the cell's exterior. The block in calcium-ion influx occurs through the activation of acidic sphingomyelinase and the release of ceramide, a metabolite that can also induce cell death.     

Presynaptic AMPA receptors: more than just ion channels?

AMPA receptor ion channels are of paramount importance for postsynaptic excitation. Several reports demonstrate that AMPA receptors are present in the presynaptic compartment and point to a role of these receptors in the modulation of presynaptic function. We discuss here the possibility that not only ion influx through the receptor, but also biochemical cascades, activated by ligand binding and independent from ion flux, might contribute to AMPA mediated presynaptic modulation.     

Vascular patterning: xylem or phloem?

Xylem and phloem are the major conduits for the transport of water and solutes through the plant. Recent work has helped to elucidate the mechanisms that determine the identity and arrangement of these two tissues.     

Root patterning: does auxin provide positional cues?

Patterning of Arabidopsis roots is mediated by cell-cell interactions, information flowing from differentiated to immature cells. The plant growth regulator auxin has now been shown to be involved in organizing the distal end of the root apex, including the extent and pattern of cell division programs and specification of cell identity.     

Bacteriophages and pathogenicity: more than just providing a toxin?

An increasing number of pathogenicity factors carried by bacteriophages have been discovered. This review considers bacteriophage-bacterium interaction and its relation to disease processes. We discuss the search for new bacteriophage-associated pathogenicity factors, with emphasis on recent advances brought by the use of genomic sequence data and the techniques of genomic epidemiology.     

Is canalization more than just a beautiful idea?

The heat-shock protein 90 (Hsp90) is currently thought to buffer eukaryotic cells against perturbations caused by pre-existing cryptic genetic variation. A new study suggests that the buffering function of Hsp90 could instead be due to its repression of de novo transposon-mediated mutagenesis.     

Bacterial Type II protein export and pilus biogenesis: more than just homologies?

Protein export by Gram-negative bacteria requires devoted machineries to allow for the passage of hydrolytic enzymes and toxins through the cell envelope. The Type II export machinery has a number of distinct characteristics, which include its role as an extension of Sec-dependent secretion, its ability to recognize and export fully folded substrates efficiently and, perhaps most significantly, the relationship between a subset of its gene products with the Type IV pilus-biogenesis apparatus. An important question is whether we can extrapolate our knowledge, albeit limited, of Type IV pilus biogenesis to understand the structure and function of the Type II export apparatus. This and other questions relating to the energetics of assembly and specificity of the apparatus are addressed in this article.     

Plant-endophyte-herbivore interactions: More than just alkaloids?

A recent paper by Rasmussen et al., (New Phytol 2007; 173:787–97) describes the interactions between Lolium perenne cultivars with contrasting carbohydrate content and the symbiotic fungal endophyte Neotyphodium lolii at different levels of nitrogen supply. In a subsequent study undertaken by Rasmussen et al., (Plant Physiol 2008; 146:1440–53) 66 metabolic variables were analysed in the same material, revealing widespread effects of endophyte infection, N supply and cultivar carbohydrate content on both primary and secondary metabolites. Here, we link insect numerical responses to these metabolic responses using multiple regression analysis.Key words: Neotyphodium lolii, Lolium perenne, high sugar grasses, metabolomics, insect herbivoresPasture grasses are often infected with symbiotic fungal endophytes and benefits for host plants arising out of these associations are generally ascribed to endophyte produced anti-herbivorous alkaloids. We tested the effects of (i) infection with three strains of endophytes differing in their alkaloid profiles, (ii) high vs. low nitrogen (N) supply, and (iii) ryegrass cultivars with high vs. control levels of water soluble carbohydrates (WSCs) on numerical insect responses (aphids, thrips, mites). A difference in WSC content between the cultivars had no significant effect on insect numbers, whereas high N compared to low N supply increased mites, thrips and alate Rhopalosiphum spp., but decreased apterous Rhopalosiphum spp. The effect of endophyte infection was strain dependant and differed for the different insects.A total of 66 metabolic variables of the same plants analysed prior to insect treatment were linked to insect responses using multiple regression analysis. One of the major conclusions to be drawn is that alkaloids are not always the most important factor influencing numerical insect responses which will also be determined by other metabolites, clearly indicating the importance of metabolomics type studies to point the way toward a mechanistic explanation of grass-endophyte-herbivore interactions.Grass species are often hosts of symbiotic clavicipitaceous endophytic fungi¹ residing in the apoplastic spaces of above ground plant parts and usually not causing any visible symptoms of infection.^2–4 These fungal symbionts confer protection from insect herbivory to their host plants through alkaloids,^5–8 some of which (ergovaline, lolitrem B) are also toxic to grazing mammals.^9,10 Natural endophyte strains lacking these mammalian toxins, but still retaining at least some of their insect deterring features, have been commercialized and are now widely used in ryegrass and tall fescue based pastures.^11,12     

The ins and outs of tubulin acetylation: more than just a post-translational modification?

Microtubules are highly dynamic polymers of α/β tubulin heterodimers that play key roles in cell division and in organizing cell cytoplasm. Although they have been discovered more than two decades ago, tubulin post-translational modifications recently gained a new interest as their role was increasingly highlighted in neuron differentiation and neurodegenerative disorders. Here, we specifically focus on tubulin acetylation from its discovery to recent studies that provide new insights into how it is regulated in health and disease and how it impacts microtubule functions. Even though new mechanisms involving tubulin acetylation are regularly being uncovered, the molecular links between its location inside the microtubule lumen and its regulators and effectors is still poorly understood. This review highlights the emerging roles of tubulin acetylation in multiple cellular functions, ranging from cell motility, cell cycle progression or cell differentiation to intracellular trafficking and signalling. It also points out that tubulin acetylation should no longer be seen as a passive marker of microtubule stability, but as a broad regulator of microtubule functions.     

Synaptic plasticity in cephalopods; more than just learning and memory?

The outstanding behavioural capacity of cephalopods is underpinned by a highly sophisticated nervous system anatomy and neural mechanisms that often differ significantly from similarly complex systems in vertebrates and insects. Cephalopods exhibit considerable behavioural flexibility and adaptability, and it might be expected that this should be supported by evident cellular and synaptic plasticity. Here, we review what little is known of the cellular mechanisms that underlie plasticity in cephalopods, particularly from the point of view of synaptic function. We conclude that cephalopods utilise short-, medium-, and long-term plasticity mechanisms that are superficially similar to those so far described in vertebrate and insect synapses. These mechanisms, however, often differ significantly from those in other animals at the biophysical level and are deployed not just in the central nervous system, but also to a limited extent in the peripheral nervous system and neuromuscular junctions.     

Regenerative medicine for the treatment of spinal cord injury: more than just promises?

Spinal cord injury triggers a complex set of events that lead to tissue healing without the restoration of normal function due to the poor regenerative capacity of the spinal cord. Nevertheless, current knowledge about the intrinsic regenerative ability of central nervous system axons, when in a supportive environment, has made the prospect of treating spinal cord injury a reality. Among the range of strategies under investigation, cell‐based therapies offer the most promising results, due to the multifactorial roles that these cells can fulfil. However, the best cell source is still a matter of debate, as are clinical issues that include the optimal cell dose as well as the timing and route of administration. In this context, the role of biomaterials is gaining importance. These can not only act as vehicles for the administered cells but also, in the case of chronic lesions, can be used to fill the permanent cyst, thus creating a more favourable and conducive environment for axonal regeneration in addition to serving as local delivery systems of therapeutic agents to improve the regenerative milieu. Some of the candidate molecules for the future are discussed in view of the knowledge derived from studying the mechanisms that facilitate the intrinsic regenerative capacity of central nervous system neurons. The future challenge for the multidisciplinary teams working in the field is to translate the knowledge acquired in basic research into effective combinatorial therapies to be applied in the clinic.     

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.     

Participation of endoplasmic reticulum and mitochondrial calcium handling in apoptosis: more than just neighborhood?

Over the past few years, extensive progress has been made in elucidating the role of calcium in the signaling of apoptosis. This has led to the characterization of calcium's role in the induction of apoptosis and in the regulation of effector proteases. In this review, we attempt to summarize the current knowledge regarding a segment of these studies, the interaction between the endoplasmic reticulum (ER) and mitochondria. This interface has been shown to play a crucial role in transferring agonist induced Ca(2+) signals to mitochondria during physiological processes. Recent evidence, however, extended the role of this Ca(2+) transfer to apoptotic pathways, showing that modulation of mitochondrial Ca(2+) uptake from the ER side has a prominent role in modulating cellular fate.     

Metabolomics analysis of the Lolium perenne–Neotyphodium lolii symbiosis: more than just alkaloids?

Above ground plant parts of Lolium perenne often harbour endophytic Neotyphodium lolii fungi. These occur both naturally and commercially, as variant strains are introduced to modify the grass metabolic profile. They reside in the apoplastic spaces and rarely cause visible symptoms of infection. The vast majority of literature has focussed on the biosynthesis, accumulation, and ecological relevance of a limited number of alkaloids produced by N. lolii which have been shown to negatively affect insect pests and vertebrate herbivores. Much less is known about the effects of other metabolites in these interactions or the role of resource supply on metabolic profiles, nor critically on the metabolic consequences of differences in the amount (concentration) of endophyte present. Here, we provide a synthesis of some of our recently published studies on effects of resource supply (nitrogen, carbohydrates) on concentrations of endophytes and endophyte specific metabolites in the L. perenne–N. lolii association. We present results of both quantitative PCR and targeted metabolomics studies, using contrasting endophyte strains in two perennial ryegrass cultivars. We also present and discuss a hypothetical schematic representation of possible links between plant and fungal metabolic networks. A multiple regression analysis of numerical insect responses and metabolic profiles indicates that effects of endophyte infection on insect population sizes could be predicted by concentrations of a range of metabolites other than alkaloids and depended on insect species, fungal strain, and nitrogen supply.     

Multifunctionality of plant ABC transporters – more than just detoxifiers

The ABC-transporter superfamily is one of the largest protein families, and members can be found in bacteria, fungi, plants and animals. The first reports on plant ABC transporters showed that they are implicated in detoxification processes. The recent completion of the genomic sequencing of Arabidopsis thaliana (L.) Heynh. [Arabidopsis Genome Initiative (2000) Nature 408:796-815] showed that Arabidopsis contains more than 100 ABC-type proteins; 53 genes code for so-called full-size transporters, which are large proteins of about 150 kDa consisting of two hydrophobic and two hydrophilic domains. The large number of genes in the MDR/MRP and PDR5-like sub-clusters and the strong sequence homology found in many cases suggest functional redundancy. One reason for the high number of genes can be attributed to the duplication of large segments of Arabidopsis chromosomes. Recent results indicate that the function of this protein family is not restricted to detoxification processes. Plant ABC transporters have been demonstrated to participate in chlorophyll biosynthesis, formation of Fe/S clusters, stomatal movement, and probably ion fluxes; hence they may play a central role in plant growth and developmental processes.