Table of Contents

Volume 5, Issue 1

  January/February 2012

  Pages 1 - 110

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VIEW POINT

Open Access Article

The magical number four: A biological, historical and mythological enigma

Hans J. Gross
Pages 1 - 2
Abstract | Full Text | PDF

Precise recognition of small object numbers without counting is a widespread phenomenon. It is well documented for humans and for a series of non-human vertebrates. Recently this has been confirmed for an invertebrate, the honeybee.¹ This type of inborn numerical competence has been named “subitizing”, from the Latin subito = suddenly, immediately. It differs from the classical, sequential counting which has to be trained, starting with the help of our fingers. For humans it had been established since 1871 by Jevons² that only up to four objects are precisely recognized and memorized. Under conditions which do not allow sequential counting, mistakes start to occur in case of more than four objects. This result has been confirmed whenever the range of visual attention has been carefully tested under a variety of rigorous conditions. It provides the basis for a novel hypothesis about the evolution of counting and numbering systems in ancient civilizations.³  




CONCEPT PAPER

Open Access Article

Social biases determine spatiotemporal sparseness of ciliate mating heuristics

Kevin B. Clark
Pages 3 - 11
Abstract | Full Text | PDF

Ciliates become highly social, even displaying animal-like qualities, in the joint presence of aroused conspecifics and nonself mating pheromones. Pheromone detection putatively helps trigger instinctual and learned courtship and dominance displays from which social judgments are made about the availability, compatibility, and fitness representativeness or likelihood of prospective mates and rivals. In earlier studies, I demonstrated the heterotrich Spirostomum ambiguum improves mating competence by effecting preconjugal strategies and inferences in mock social trials via behavioral heuristics built from Hebbian-like associative learning. Heuristics embody serial patterns of socially relevant action that evolve into ordered, topologically invariant computational networks supporting intra- and intermate selection. S. ambiguum employs heuristics to acquire, store, plan, compare, modify, select, and execute sets of mating propaganda. One major adaptive constraint over formation and use of heuristics involves a ciliate’s initial subjective bias, responsiveness, or preparedness, as defined by Stevens’ Law of subjective stimulus intensity, for perceiving the meaningfulness of mechanical pressures accompanying cell-cell contacts and additional perimating events. This bias controls durations and valences of nonassociative learning, search rates for appropriate mating strategies, potential net reproductive payoffs, levels of social honesty and deception, successful error diagnosis and correction of mating signals, use of insight or analysis to solve mating dilemmas, bioenergetics expenditures, and governance of mating decisions by classical or quantum statistical mechanics. I now report this same social bias also differentially affects the spatiotemporal sparseness, as measured with metric entropy, of ciliate heuristics. Sparseness plays an important role in neural systems through optimizing the specificity, efficiency, and capacity of memory representations. The present findings indicate sparseness performs a similar function in single aneural cells by tuning the size and density of encoded computational architectures useful for decision making in social contexts.




SHORT COMMUNICATIONS

Open Access Article

Co-regulation of the arf-activation cycle and phospholipid-signaling during golgi maturation

Yvonne Gloor, Thomas Müller-Reichert and Christiane Walch-Solimena
Pages 12 - 15
Abstract | Full Text | PDF

The Golgi apparatus is the central protein sorting station inside eukaryotic cells. Although many regulators of Golgi trafficking have been identified, little is known about their crosstalk. Both the Arf activation cycle and phosphatidylinositol 4-phosphate metabolism have been recognized as key processes in the regulation of vesicular transport from this organelle. However, the mechanism ensuring the proper co-regulation of these processes has eluded our understanding thus far. We recently identified a physical interaction between the late yeast Golgi Arf activator Sec7p and the PI4-kinase Pik1p, and showed that the two proteins cooperate in the formation of clathrin-coated vesicles. This finding gives the first insight on the coordinated generation of a dual key signal by a small GTPase and a signaling phospholipid at the Golgi. In addition, it opens new perspectives for a better understanding of Golgi maturation through coordinated regulation of highly dynamic lipid and protein composition of this organelle.

Open Access Article

Visualizing the high curvature regions of post-mitotic nascent nuclear envelope membrane

Lei Lu and Tomas Kirchhausen
Pages 16 - 18
Abstract | Full Text | PDF

We previously reported that mitotic endoplasmic reticulum (ER) membrane cisternae or sheets directly assemble mammalian nuclear envelope (NE) at the end of mitosis. In this study, we investigated the dynamics of the high curvature regions of partially assembled nuclear envelope membrane using reticulon4a as a probe. We found that, after sorting out reticulon4a from the nascent NE membrane sheets, reticulon4a is specifically localized to the leading edges. Our 3D time lapse images suggested that ER tubules could be incompetent in assembling the NE membrane. Our findings suggest a possible role of reticulons at the leading edges during the NE re-assembly and provide further evidences that the mitotic assembly of NE is by ER cisternae rather than tubules.

Open Access Article

In silico characterization of a nitrate reductase gene family and analysis of the predicted proteins from the moss Physcomitrella patens

Rigoberto Medina-Andrés and Verónica Lira-Ruan
Pages 19 - 25
Abstract | Full Text | PDF

Assimilatory nitrate reductase (NR; EC 1.7.1.1-3) catalyzes the reduction of nitrate to nitrite. This enzyme has a conserved structure common to fungi, algae and plants. However, some differences in the amino acid sequence between plant and algal NR suggest that the activity regulation mechanisms have changed during plant evolution. Since only NRs from angiosperms have been studied, the search and analysis of NR genes and proteins from the moss Physcomitrella patens, a basal land plant, was performed to widen the knowledge of land plant NR structure. A family of three nr genes, named ppnia1;1, ppnia1;2 and ppnia2, was localized in the P. patens genome. The predicted proteins are canonical NRs with the conserved domains Molybdene-Cytochorme b –Cytochrome b reductase and possess 20 amino acid residues important for the enzymatic function conserved in plant and algal NRs. Interestingly, moss NRs lack a consensus sequence, common to angiosperm NRs, that is a target for posttranslational regulation. A phylogenetic tree with embryophyte and green algae NR sequences was constructed and P. patens NRs localized at the base of embryophyte NR evolution. The data presented here suggest that bryophytes and vascular plants have different systems to regulate NR activity.

Open Access Article

Is cohesin required for spindle-pole-body/centrosome cohesion?

Hui Jin, Martin Avey and Hong-Guo Yu
Pages 26 - 29
Abstract | Full Text | PDF

Centrosomes are microtubule-organizing centers that nucleate spindle microtubules during cell division. In budding yeast, the centrosome, often referred to as the spindle pole body, shares structural components with the centriole, the central core of the animal centrosome. The parental centrosome is duplicated when DNA replication takes place. Like sister chromatids tethered together by cohesin, duplicated centrosomes are linked and then separate to form the bipolar spindle necessary for chromosome segregation. Recent studies have shown that cohesin is also localized to the animal centrosome and is perhaps directly involved in engaging paired centrioles. Here we discuss the potential role of cohesin in mediating spindle-pole-body cohesion in the context of yeast meiosis. We propose that the coordination of chromosome segregation with centrosome cohesion and duplication is mediated by the antagonistic interaction between the Aurora kinase and the Polo kinase and that the role of cohesin in centrosome regulation appears to be indirect in budding yeast.




MINI-REVIEWS

Open Access Article

High pressure, a tool to switch between soluble and fibrillar prion protein structures

Joan Torrent and Reinhard Lange
Pages 30 - 33
Abstract | Full Text | PDF

The native soluble as well as different aggregated states of recombinant prion proteins are highly sensitive to high pressure. On the one hand, its application to the native α-helical protein induces reversibly a metastable structure that relaxes to amyloid fibrils after prolonged incubation. On the other hand, its application to synthetic prion amyloid fibrils leads to partial disaggregation into native monomers as well as to proto-filaments that have lost several amyloid features. In addition, heat-induced β-sheet prion protein aggregates are dissolved and revert into α-helical monomers by applying high pressure. This profound pressure sensitivity of prion protein structure is explained by large volume differences of the different structural states. Hence, pressure appears as a suitable thermodynamic parameter for exploring the highly complex conformational landscape of prion protein. Its further analysis should help identifying prion protein structural states that are on the pathogenic pathway.

Open Access Article

The maintenance of mitochondrial genetic stability is crucial during the oncogenic process

Pablo Iglesias, Antonio Salas and Jose A. Costoya
Pages 34 - 38
Abstract | Full Text | PDF

The main energetic resources of the cell are the mitochondria. As such, these organelles control a number of processes related to the life and death of the cell and also have a prominent function in the maintenance of tumor cells. In the last years, several authors have proposed an active role for mitochondria in tumorigenesis, more specifically concerning somatic mutations in mitochondrial DNA (mtDNA). Here, we wanted to evaluate this hypothesis based on the conclusions obtained in a model of gliomagenesis with elevated levels of ROS (reactive oxygen species), a toxic by-product of tumor metabolism. According to our findings, none of the mtDNA variants were found relevant to the tumoral process or suggest the involvement of mitochondria in tumorigenesis beyond the metabolic requirements of the tumoral cell. We conclude that there is not enough evidence to support the claim that mitochondrial instability holds any relevant role in the tumoral process.

Open Access Article

Active actin gels

Shahid M. Khan, Rehan Ali, Nimra Asi and Justin E. Molloy
Pages 39 - 42
Abstract | Full Text | PDF

The self-organization of actin filaments is a topic that links cell biology with condensed matter physics. In vitro assays allow precise manipulation of component mechanical and chemical properties, needed for rigorous tests of theoretical models. We review recent work on in vitro motility assays that documented emergence of ordered actin filament microdomains powered by myosin motor proteins at high filament densities. Motor and filament surface density and mechanochemical cycle kinetics are additional parameters under current investigation. Individual filament collisions have been studied in order to elucidate the emergent population behavior. Apolar, weak  interactions evidenced by local filament deformations during crossover events are attenuated at high motor densities. Theoretical analysis requires refinement of rigid rod filament models. In intact cells, accessory proteins modulate actin filament length, bundling or sliding and this gives rise to complex emergent structures and behaviors such as cell motility and chemotaxis. The development of generic, mechanical and biochemical frameworks with predictive power that link molecular properties with micro- and macroscopic phenomena seen in living cells requires dialogue between theoreticians and experimentalists.

Open Access Article

Hitching a ride: Vector feeding and virus transmission

Candice A. Stafford, Gregory P. Walker and Diane E. Ullman
Pages 43 - 49
Abstract | Full Text | PDF

The majority of plant viruses rely on insect vectors for transmission. Insects with piercing-sucking mouthparts are the most common and efficient vectors because, they are able to inject viruses into specific plant tissues. Acquisition and inoculation of viruses occurs during specific vector feeding behaviors, and feeding behavior varies greatly among insects with piercing-sucking mouthparts. In this review we provide an overview of the feeding behavior of the major insect vectors with piercing sucking mouthparts: aphids, whiteflies, mealybugs, hoppers, and thrips. We briefly review the different mechanisms of plant virus transmission by these insects, and discuss how each mechanism requires a vector that engages in specific feeding behaviors, and how differences in feeding behavior among these insects can determine which viruses they are capable of transmitting. We also discuss recent findings indicating that plant viruses can directly modify their vector's behavior in a way that enhances transmission to a host plant.




REVIEW

Open Access Article

Vesicle formation within endosomes: An ESCRT marks the spot

Jonathan R. Mayers and Anjon Audhya
Pages 50 - 56
Abstract | Full Text | PDF

Vesicle-mediated cargo transport within the endomembrane system requires precise coordination between adaptor molecules, which recognize sorting signals on substrates, and factors that promote changes in membrane architecture. At endosomal compartments, a set of protein complexes collectively known as the ESCRT machinery sequesters transmembrane cargoes that harbor a ubiquitin modification and packages them into vesicles that bud into the endosome lumen. Several models have been postulated to describe this process. However, consensus in the field remains elusive. Here, we discuss recent findings regarding the structure and function of the ESCRT machinery, highlighting specific roles for ESCRT-0 and ESCRT-III in regulating cargo selection and vesicle formation.




ARTICLE ADDENDA

Open Access Article

Fitness costs associated with chemical signaling

Sandra Steiger, Tobias Meier and Josef K. Müller
Pages 57 - 60
Abstract | Full Text | PDF

The production, maintenance and transmission of chemical signals often entail costs. Costs can arise, for instance, if signal production depends on the availability of limited nutritional resources or if signal transmission leads to attraction of predators. Many species effectively reduce these costs by signaling at specific times or in certain contexts only. We previously reported that breeding burying beetle females facultatively adjust their pheromone emission in response to their social environment, emitting high amounts of their chemical signal in the presence of a male partner, but not when providing uniparental care. Here we present data showing that chemical signaling is costly, and that higher investments in signaling result in reduced clutch sizes, but not a shorter life span, in the burying beetle Nicrophorus vespilloides.

Open Access Article

Molecular control of compound Exocytosis: A key role for VAMP8

Peter Thorn and Herbert Gaisano
Pages 61 - 63
Abstract | Full Text | PDF

Exocytosis is the process of fusion of a membrane-bound vesicle with the cell membrane and subsequent release of the vesicle content to the outside. It is now widely accepted that SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) proteins are key components in the molecular machinery of exocytosis. SNARE proteins on the vesicle membrane selectively form complexes with specific SNAREs on the cell membrane. In a variant of exocytosis, called compound exocytosis, secretory vesicles still fuse with the cell membrane but vesicle-to-vesicle fusion enhances secretory output. Two types of compound exocytosis occur, either vesicles fuse with each other and then fuse with the cell membrane, or a vesicle fuses with the cell membrane and then becomes a target for further vesicles to fuse with it. It is expected that SNAREs are important for vesicle-to-vesicle fusion but the mechanism(s) that control these processes is unknown. In our recent paper (Behrendorff et al. 2011) we provide evidence that VAMP8 (a Q-SNARE) is essential in regulating compound exocytosis. Here we discuss the implications of our findings with reference to a new model for the control of vesicle-to-vesicle fusion.

Open Access Article

Munc13-4*rab27 complex tethers secretory lysosomes at the plasma membrane

Edo D. Elstak, Maaike Neeft, Nadine T. Nehme, Isabelle Callebaut, Geneviève de Saint Basile and Peter van der Sluijs
Pages 64 - 67
Abstract | Full Text | PDF

Natural Killer (NK) cells and Cytotoxic T lymphocytes (CTL) are critical for the immune response against virus infections or transformed cells. They kill target cells via polarized exocytosis of lytic proteins from secretory lysosomes (SL). Rab27a and munc13-4 interact directly and are required for target cell killing. How they cooperate in the intricate degranulation process is not known. We identified critical residues in munc13-4 for rab27 interaction and tested binding mutants in several complementation assays. In a rat mast cell line we replaced endogenous munc13-4 with ectopically expressed munc13-4 constructs. Unlike wild type munc13-4, binding mutants fail to rescue β-hexosaminidase secretion. In accord, expression of binding mutants in CTL of Familial Hemophagocytic Lymphohistiocytosis type 3 patients, does not rescue CD107 appearance on the plasma membrane. Total Internal Reflection Fluorescence (TIRF) imaging shows that munc13-4*rab27a restricts motility of SL in the subapical cytoplasm. We propose that rab27*munc13-4 tethers SL to the plasma membrane, a requirement for formation of a cognate SNARE complex for fusion.

Open Access Article

Endocannabinoid-binding CB1 and TRPV1 receptors as modulators of sperm capacitation

Nicola Bernabò, Paola Palestini, Marco Chiarini, Mauro Maccarrone, Mauro Mattioli and Barbara Barboni
Pages 68 - 70
Abstract | Full Text | PDF

Mammalian spermatozoa reach the ability to fertilize only after they complete a complex series of physical-chemical modification, the capacitation. Recently, the endocannabinoid-binding type-1cannabinoid receptor (CB1) and transient receptor potential vanilloid 1 (TRPV1) channel have been proposed to play a key role in the control of capacitation. In particular CB1, acting via a Gi protein/cAMP/PKA pathway, maintains low cAMP levels in early stages of post ejaculatory life of male gametes. By this way it promotes the maintenance of membrane stability, thus avoiding the premature fusion of plasma membrane (PM) and outer acrosome membrane (OAM), which is mandatory for the exocytosis of acrosome content. TRPV1, on the contrary, becomes active during the latest stages of capacitation, and allows the rapid increase in intracellular calcium concentration that leads to the removal of the F-actin network interposed between PM and OAM, leading to their fusion and, ultimately, to the acrosome reaction.

Open Access Article

The extracellular matrix remodeled: Interdependency of matrix proteolysis, cell adhesion, and force sensing

Robert Kirmse, Hannes Otto and Thomas Ludwig
Pages 71 - 73
Abstract | Full Text | PDF

Membrane Type-1 Matrix Metalloproteinase (MT1-MMP, MMP-14) is regarded as the prototype of a membrane- tethered protease. It drives fundamental biological processes ranging from embryogenesis to cancer metastasis. The proteolytic cleavage of proteins by MT1-MMP can rapidly alter the biophysical properties of a cell’s microenvironment. Cell’s must thus be able to sense and react to these alterations and transduce these effectively in biochemical signals and cell responses. Although many cells react as acutely to such physical stimuli as they do to chemical ones, the regulatory effects of these have been less extensively explored. In order to investigate a possible interdependency of proteolytic matrix cleavage by MT1-MMP and the generation and sensing of force by cells, a model system was established which exploits the properties of a matrix array of parallel collagen-I fibers. The resulting an-isotropy of the matrix with high tensile strength along the fibers and high mobility perpendicular to it allows the convenient detection of bundling and cleavage of the collagen fibers, as well as spreading and durotaxis of the cells. In summary, we have demonstrated that cell adhesion, force generation, and force sensing are vital for the regulation of MT1-MMP for efficient cleavage of collagen-I.

Open Access Article

Munc18–1, exocytotic fusion pore regulation and local membrane anisotropy

Jernej Jorgačevski and Robert Zorec
Pages 74 - 77
Abstract | Full Text | PDF

The release of hormones and neurotransmitters from vesicles can be modified by the regulation of the fusion pore, an aqueous channel that forms upon the fusion of the vesicle membrane with the plasma membrane. However, the mechanisms are unclear. Munc18–1 protein interacts with Syntaxin1 (Synt 1), a member of the SNARE proteins, which plays an important role in exocytosis. It has been shown that Munc18–1 has multiple roles, both in pre- and post-fusion stages of exocytosis. It regulates the traffic of Synt1 to the plasma membrane. By inhibiting the tethering of the vesicle SNARE protein Synaptobrevin 2 (Syb2) solely to Synt1 at the plasma membrane, but favoring the vesicular tethering to the preformed binary cis SNARE complex of Synt1A-SNAP25B, Munc18–1 is tuning vesicle docking and the membrane merger process. Additionally, Munc18–1 affects exocytosis at the post-fusion stage by regulating the fusion pore properties (i.e., dwell-time and fusion pore diameter). Among many possible mechanisms that may regulate the fusion pore, but have never been considered previously, is the influence of Munc18–1 on the membrane anisotropy, which determines the local spontaneous membrane curvature and the architecture of the fusion pore. We here propose that Munc18–1 affects the fusion pore by modulating the dynamic local (re)arrangement of anisotropic membrane components within the highly curved fusion pore nanostructure, to which proteins, lipids or their complexes can participate.

Open Access Article

Uncovering the complexity of ant foraging trails

Tomer J. Czaczkes, Christoph Grüter, Sam M. Jones and Francis L.W. Ratnieks
Pages 78 - 80
Abstract | Full Text | PDF

The common garden ant Lasius niger use both trail pheromones and memory of past visits to navigate to and from food sources. In a recent paper we demonstrated a synergistic effect between route memory and trail pheromones: the presence of trail pheromones results in experienced ants walking straighter and faster. We also found that experienced ants leaving a pheromone trail deposit less pheromone. Here we focus on another finding of the experiment: the presence of cuticular hydrocarbons (CHCs), which are used as home range markers by ants, also affects pheromone deposition behavior. When walking on a trail on which CHCs are present but trail pheromones are not, experienced foragers deposit less pheromone on the outward journey than on the return journey. The regulatory mechanisms ants use during foraging and recruitment behavior is subtle and complex, affected by multiple interacting factors such as route memory, travel direction and the presence trail pheromone and home-range markings.

Open Access Article

Contribution of mitochondrial network dynamics to intracellular ROS signaling

Junseong Park and Chulhee Choi
Pages 81 - 83
Abstract | Full Text | PDF

Oxidative stresses can induce rapid depolarization of inner mitochondrial membrane potential and subsequent impairment of oxidative phosphorylation. Damaged mitochondria produce more reactive oxygen species (ROS), particularly the superoxide anion (O2-) and hydrogen peroxide (H₂O₂), which potentiate mitochondria-driven ROS propagation, so-called ROS-induced ROS release (RIRR), via activation of an inter-mitochondrial signaling network. In this context, mitochondrial network dynamics, such as their density, number, and spatial distribution, can affect mitochondria-driven ROS propagation. To investigate this inter-mitochondrial communication, we developed a mathematical model using an agent-based modeling approach, and tested the effect of mitochondrial network dynamics on RIRR for mitochondria under various conditions. Simulation results show that mitochondrial network dynamics are critical determinants of inter-mitochondrial ROS signaling patterns and main messenger ROS molecules. We further elucidated the potential mechanism of these actions, which is conversion of major messenger molecules involved in ROS signaling. Collectively, we propose that mitochondrial network dynamics can determine cellular responses to oxidative stress by switching the molecular species involved in cellular signaling.

Open Access Article

Linking differences in membrane tension with the requirement for a contractile actomyosin scaffold during exocytosis in salivary glands

Andrius Masedunskas, Natalie Porat-Shliom and Roberto Weigert
Pages 84 - 87
Abstract | Full Text | PDF

In all the major secretory organs regulated exocytosis is a fundamental process that is used for releasing molecules in the extracellular space. Molecules destined for secretion are packaged into secretory vesicles that fuse with the plasma membrane upon the appropriate stimulus. In exocrine glands, large secretory vesicles fuse with specialized domains of the plasma membrane, which form ductal structures that are in direct continuity with the external environment and exhibit various architectures and diameters. In a recent study, we used intravital microscopy to analyze in detail the dynamics of exocytic events in the salivary glands of live rodents under conditions that cannot be reproduced in in vitro or ex vivo model systems. We found that after the opening of the fusion pore large secretory vesicles gradually collapse with their limiting membranes being completely absorbed into the apical plasma membrane canaliculi within 40–60 sec. Moreover, we observed that this controlled collapse requires the contractile activity of actin and its motor myosin II, which are recruited onto the large secretory vesicles immediately after their fusion with the plasma membrane. Here we suggest that the actomyosin complex may be required to facilitate exocytosis in those systems, such as the salivary glands, in which the full collapse of the vesicles is not energetically favorable due to a difference in membrane tension between the large secretory vesicles and the canaliculi.

Open Access Article

Intracellular signaling controlled by the endosomal-exosomal pathway

Frederik J. Verweij, Jaap M. Middeldorp and D. Michiel Pegtel
Pages 88 - 93
Abstract | Full Text | PDF

Tight control of intracellular signaling is essential for developmental processes such as cell differentiation, migration but also for maintaining tissue homeostasis. Disruption in the control of these signaling pathways can result in cell death (apoptosis), anergy or uncontrolled cell proliferation and growth leading to cancer. In multicellular organisms, timely termination of signaling is thus equally important as initiation. Known pathways for downregulating membrane receptor-mediated signaling are mediated via specialized endosomal organelles known as lysosomes and proteosomes that degrade such proteins in the cytoplasm. An alternative pathway for attenuating receptor-mediated signaling was recently discovered independently by the group of M. Caplan and our own group.1,2 It appears that apart from the classical protein degradation machineries, the release of signaling proteins also effectively restricts signaling of at least two major signal transduction routes; the canonical Wnt/β-catenin and NFκB pathways. Expelling proteins from the cell, rather than coordinated degradation in lysosomes may involve defined protein modifications, such as ubiquitination, myristyolation, and/or palmitoylation, but little experimental data are currently available. Although the secretion of proteins via exosomes starts by accumulation within multivesicular bodies (MVBs), a key distinction with degredatory MVBs is that exosome-producing MVBs seem to preferentially fuse with the plasmamembrane (Fig. 1). Here we discuss the latest developments in the biology of exosomes and their unexpected effect on intracellular signal transduction.

Open Access Article

The interaction of Hsc70 protein with fibrillar α-Synuclein and its therapeutic potential in Parkinson’s disease

Samantha Pemberton and Ronald Melki
Pages 94 - 95
Abstract | Full Text | PDF

We recently described the effect of the constitutively expressed chaperone, Hsc70 protein, on α‑Synuclein aggregation, a phenomenon associated with Parkinson disease. In vitro, Hsc70 binds to soluble α‑Syn and slows down its assembly into fibrils. Hsc70 also binds fibrillar α‑Syn, 5-fold tighter than soluble α‑Syn. This interaction reduces the cytotoxicity associated with naked α‑Syn fibrils. Herein, we discuss the feasibility of engineering a “minichaperone” which could be used against α‑Syn assembly propagation in Parkinson disease: taking what is necessary and sufficient within Hsc70 to protect against the damaging repercussions of high molecular weight α‑Syn species’ passage from one neuron to another in the brain.

Open Access Article

Quorum sensing-controlled buoyancy through gas vesicles: Intracellular bacterial microcompartments for environmental adaptation

Joshua P. Ramsay and George P. C. Salmond
Pages 96 - 98
Abstract | Full Text | PDF

Gas vesicles are gas-filled microcompartments produced by many cyanobacteria and haloarchaea to regulate buoyancy and control positioning in the water column. Recently we identified the first case of gas vesicle production by a member of the Enterobacteriaceae, Serratia sp ATCC39006. Gas vesicle production enabled colonisation of the air-liquid interface and was positively regulated in low-oxygen conditions, suggesting development of these intracellular organelles is an adpative mechanism facilitating migration to the water surface. Vesicle production was also regulated by the intercellular communication molecule N‑butanoyl-L‑homoserine lactone (BHL) showing that gas vesicle production is controlled at the population level, through quorum sensing, with BHL acting as a morphogen. Gas vesicle production was also reciprocally regulated with flagella-driven swarming motility by the global regulatory protein RsmA, suggesting a fork in the regulatory pathway that controls induction of these distinct modes of mobility. Here we discuss these findings in the context of the interesting physiology of Serratia 39006 and highlight future prospects for gas vesicle research in this highly tractable strain.

Open Access Article

Rho proteins crosstalk via RhoGDIalpha: At random or hierarchically ordered?

Audrey Stultiens, T. T. Giang Ho, Betty V. Nusgens, Alain C. Colige and Christophe F. Deroanne
Pages 99 - 101
Abstract | Full Text | PDF

The small GTPases of the Rho family are key signaling molecules regulating a plethora of biological pathways. They can exert diverse, sometimes opposite, contributions to specific cellular processes explaining why their regulation and their crosstalk must be finely tuned. Several mechanisms driving crosstalk between Rho GTPases have been described in the literature. They implicate proteins regulating their activity or common downstream effectors. Among the proteins regulating Rho GTPases cycling, RhoGDIs were viewed until very recently as passive inhibitors. Here, we will focus on recent data supporting a role for RhoGDIalpha in the crosstalk between RhoGTPases and present our results suggesting that “preferential” RhoGDIalpha-mediated crosstalk takes place between closely related Rho GTPases.

Open Access Article

Genomics of Megavirus and the elusive fourth domain of Life

Matthieu Legendre, Defne Arslan, Chantal Abergel and Jean-Michel Claverie
Pages 102 - 106
Abstract | Full Text | PDF

We recently described Megavirus chilensis, a giant virus isolated off the coast of Chile, also replicating in fresh water acanthamoeba. Its 1,259,197-bp genome encodes 1,120 proteins and is the largest known viral genome. Megavirus and its closest relative Mimivirus only share 594 orthologous genes, themselves sharing only 50% of identical residues in average. Despite this divergence, comparable to the maximal divergence exhibited by bacteria within the same division (e.g., gamma proteobacteria), Megavirus retained all of the genomic features unique to Mimivirus, in particular its genes encoding key-elements of the translation apparatus, a trademark of cellular organisms. Besides homologs to the four aminoacyl-tRNA synthetases (aaRS) encoded by Mimivirus, Megavirus added three additional ones, raising the total of known virus-encoded aaRS to seven: IleRS, TrpRS, AsnRS, ArgRS, CysRS, MetRS, TyrRS. This finding strongly suggests that large DNA viruses derived from an ancestral cellular genome by reductive evolution. The nature of this cellular ancestor remains hotly debated.

Open Access Article

Protein misfolding and clearance in demyelinating peripheral neuropathies: Therapeutic implications

Samuel M. Lee, Lih-Shen Chin and Lian Li
Pages 107 - 110
Abstract | Full Text | PDF

Peripheral neuropathies such as Charcot-Marie-Tooth disease (CMT) are a group of neurological disorders that affect the peripheral nervous system. Although demyelinating CMT is the most prevalent hereditary peripheral neuropathy, there are currently no effective treatments for patients suffering from this disease. Recent studies by our group and others have provided a link between protein misfolding and demyelinating CMT and indicate that impairment of the proteasome and aggresome-autophagy pathways may contribute to CMT pathogenesis. These studies suggest that targeting protein quality control systems involved in cytoprotection against CMT-associated misfolded proteins could have therapeutic benefits for treating demyelinating CMT.