Table of Contents

Volume 2, Issue 3

  May/June 2009

  Pages 203 - 291

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ARTICLE ADDENDA

Open Access Article

Recognition without awareness in humans and its implications for animal models of episodic memory

Joel L. Voss and Ken A. Paller
Pages 203 - 204
http://dx.doi.org/10.4161/cib.2.3.7822
Abstract | PDF

Animal models of episodic memory—the ability to recall events from the past along with relevant spatial, temporal, and other contextual detail—have been criticized on the grounds that it is difficult to determine if animals engage in the “mental time travel” that accompanies episodic recall in humans. It is possible that animals rely on mechanisms different from those operative in humans. We have added a new dimension to these concerns by showing that a test widely considered to measure episodic memory in humans can be constructed such that it measures nonconscious (implicit) memory under certain test parameters. The same parameters are common in tests frequently used to study recognition in nonhuman animals. In particular, recognition was driven by implicit memory when (1) recognition decisions could not be guided by semantic information, and (2) decisions were made with relatively high automaticity. These findings suggest that nonhuman animals may rely on implicit memory processing in many episodic-memory testing circumstances, as semantic content is minimal and automaticity is likely after the extended practice usually required. Identifying factors that promote and discourage recognition based on implicit memory is therefore necessary for creating accurate cognitive and neurobiological models of memory processing in humans and other animals.

Open Access Article

A lattice model of the nuclear pore complex

Stephen G. Brohawn and Thomas U. Schwartz
Pages 205 - 207
http://dx.doi.org/10.4161/cib.2.3.7873
Abstract | PDF

The nuclear pore complex (NPC) is one of the largest protein machines in the cell and forms the sole conduit for nucleocytoplasmic transport in eukaryotes. The NPC is composed of an eightfold radially symmetric scaffold of architectural proteins that anchor a set of phenylalanine-glycine (FG) repeat proteins that form the transport barrier. As a step toward elucidating the molecular architecture of the NPC, we solved the structure of nucleoporin 85 (Nup85) in complex with Seh1, a module in the heptameric Nup84 subcomplex. We define a new tripartite protein element, the ancestral coatomer element ACE1, which Nup85 specifically shares with several other nucleoporins and vesicle coat proteins. We predicted and verified functional sites on nucleoporin ACE1 members based on analogy to ACE1 interactions that propagate the COPII vesicle coat. Thus, we provide the first experimental evidence for evolution of the NPC and vesicle coats from a common ancestor. We propose that the NPC structural scaffold, like vesicle coats, is a polygonal network composed of vertex and edge elements that forms a molecular lattice upon which additional nucleoporins assemble. Here we further discuss our findings and elaborate on our lattice model of the nuclear pore complex.

Open Access Article

Microtubule amplification in the assembly of mitotic spindle and the maturation of kinetochore fibers

Hui Zhu, Kayleen Fang and Guowei Fang
Pages 208 - 210
http://dx.doi.org/10.4161/cib.2.3.7875
Abstract | PDF

Efficient assembly of a mitotic spindle and stable attachment of microtubules (k-fibers) to kinetochores are essential for the high fidelity of chromosome segregation. Both spindle assembly and Mitotic spindle mediates the segregation of chromosomes in the cell cycle and the proper function of the spindle is crucial to the high fidelity of chromosome segregation and to the stability of the genome. Nucleation of microtubules (MTs) from centrosomes and chromatin represents two well-characterized pathways essential for the assembly of a dynamic spindle in mitosis. Recently, we identified a third MT nucleation pathway, in which existing MTs in the spindle acts as a template to promote the nucleation and polymerization of MTs, thereby efficiently amplifying MTs in the spindle. We will review here our current understanding on the molecular mechanism, the physiological function and the cell-cycle regulation of MT amplification.k-fiber formation require robust nucleation and polymerization of microtubules mediated by the γ-tubulin ring complex (γ TuRC). It has been well established that centrosomes and chromatin are the two centers for microtubule nucleation. We recently demonstrate a third mechanism for microtubule nucleation and polymerization, in which the existing microtubules in the spindle act as templates to promote the formation of new microtubules. We showed that a novel spindle-associated protein, FAM29A, plays a critical role in this microtubule-dependent microtubule amplification. FAM29A associates with spindle microtubules and directly interacts with and recruits NEDD1, the targeting subunit of γTuRC. Spindle-associated γTuRC then promotes microtubule nucleation required for spindle assembly and k-fiber formation. This novel microtubule amplification pathway provides a powerful mechanism to control the local cytoskeleton structures independent of centrosomes and chromatin. We speculate that microtubule amplification not only functions in mitosis, but may also act in other physiological processes to re-enforce existing cytoskeleton structures.

Open Access Article

Ativation of a built-in bacterial programmed cell death system as a novel mechanism of action of some antibiotics

Hanna Engelberg-Kulka, Idan Yelin and Ilana Kolodkin–Gal
Pages 211 - 212
http://dx.doi.org/10.4161/cib.2.3.7876
Abstract | PDF

The modes of action of antibiotics are mainly characterized by their effects on their targets. Previously,^1,2 and in a recent paper,³ we have reported our discovery of a new mechanism for the action of some antibiotics. Rather than directly interfering with a vital bacterial pathway, these antibiotics act by triggering the bacterial toxin–antitoxin chromosomal module mazEF, thereby causing the bacteria to commit suicide. We also showed that antibiotics that inhibit transcription and/or translation cause mazEF-mediated cell death by forming Reactive Oxygen Species (ROS).3 Moreover, we found that after treatment by such antibiotics, the mazEF system cannot be activated, and thus ROS cannot be formed, without the presence of communication signaling peptide called the Extracellular Death Factor (EDF). Our results challenge the classical division between bacteriostatic and bactericidal antibiotics. Our study further provides evidence that mode of action of antibiotics may also be determined by the ability of the bacteria to communicate through the signaling peptide EDF. In this Addendum article we present a model of how the presence of some antibiotics may result in this novel downstream pathway.


Open Access Article

EGF induces rapid reorganization of plasma membrane microdomains

Erik G. Hofman, Arjen N. Bader, Hans C. Gerritsen and Paul M.P. van Bergen en Henegouwen
Pages 213 - 214
http://dx.doi.org/10.4161/cib.2.3.7877
Abstract | PDF

The plasma membrane of mammalian cells is composed of a great variety of different lipids which are laterally organized into lipid domains. The segregation of lipids into domains has been studied in great detail in vesicles but domain formation of lipids in the plasma membrane of live cells is still unclear. We have previously used fluorescence lifetime imaging microscopy to study the colocalization of the receptor for EGF with the ganglioside GM1 and the GPI-anchored green fluorescent protein. Here we have used this technology to study the effect of EGF on the organization of GM1 in the plasma membrane. Our data show that stimulation of the cell with EGF induces rapidly a strong increase in colocalization of GM1 molecules, suggesting the formation of large lipid domains. These results support the notion that activation of EGFR signaling may result in the formation of signaling platforms.

Open Access Article

The mechanism of action of PA-824: Novel insights from transcriptional profiling

Ujjini Manjunatha, Helena I.M. Boshoff and Clifton E. Barry
Pages 215 - 218
http://dx.doi.org/10.4161/cib.2.3.7926
Abstract | PDF

The bicyclic nitroimidazole PA-824 is a pro-drug with a very complex mechanism of action active against both replicating and hypoxic, non-replicating Mycobacterium tuberculosis. Microarray analysis of the mode of action of PA-824 showed a puzzling mixed effect both on genes responsive to both cell wall inhibition (like isoniazid) and respiratory poisoning (like cyanide). The aerobic killing mechanism of this drug appears to involve inhibition of cell wall mycolic acid biosynthesis through an as yet unknown molecular mechanism. However, the structure-activity relationships governing aerobic activity do not parallel the relationships determining anaerobic activity. Based on the metabolite profiling of PA-824 and various derivatives by Ddn-mediated activation, we have shown that PA-824 acts directly as an NO donor.¹ This respiratory poisoning through nitric oxide release seemed to be a crucial element of anaerobic activity by PA-824. The effect of PA-824 on the respiratory complex under hypoxic non-replicating conditions was also manifested in a rapid drop in intracellular ATP levels, again similar to that observed by cyanide treatment. Thus, transcriptional profiling provided valuable clues to elucidating the molecular mechanism of mycobacterial killing.

Open Access Article

Genetic mechanism regulating bacterial cell shape and metabolism

Daisuke Shiomi, Hideo Mori and Hironori Niki
Pages 219 - 220
http://dx.doi.org/10.4161/cib.2.3.7930
Abstract | PDF

The bacterium Escherichia coli is rod-shaped, and a unit cell keeps regular dimensions of about 1.5 μm long and 0.5 μm wide. The rod-shaped cell is composed of two parts: a cylinder in the center and caps at both ends. The length of the cylinder corresponds to the length of the rod cell. A recent paper reported the genetic regulation of the cell length by rodZ. RodZ is a membrane protein with bitopic topology that assembles underneath the cell membrane to form helical filaments along the lateral axis of the cell with the bacterial actin MreB. RodZ filaments probably interact with enzymes that contribute to peptidoglycan synthesis. Cells lacking rodZ shorten only along the lateral axis of the cell so that the cells become round-shaped instead of rod-shaped. Such spheroidal cells consist only of caps due to the loss of almost all of the cylinder. In addition, carbon metabolism is remarkably disturbed by the deficiency of RodZ. This suggests that the transport of nutrients at the surface of the cylinder is reduced in rodZ mutant cells. Thus, cell morphology is also critical for proper metabolism for cell proliferation.

Open Access Article

The biological and cultural foundations of language

Morten H. Christiansen, Nick Chater and Florencia Reali
Pages 221 - 222
http://dx.doi.org/10.4161/cib.2.3.8034
Abstract | PDF

A key challenge for theories of language evolution is to explain why language is the way it is and how it came to be that way. It is clear that how we learn and use language is governed by genetic constraints. However, the nature of these innate constraints has been the subject of much debate. Although many accounts of language evolution have emphasized the importance of biological adaptations specific to language, we discuss evidence from computer simulations pointing to strong restrictions on such adaptations. Instead, we argue that processes of cultural evolution have been the primary factor affecting the evolution of linguistic structure, suggesting that the genetic constraints on language largely predate the emergence of language itself.

Open Access Article

Tubular structures in heterogeneous membranes induced by the cell penetrating peptide Penetratin

Antonin Lamazière, Gérard Chassaing, Germain Trugnan and Jesus Ayala-Sanmartin
Pages 223 - 224
http://dx.doi.org/10.4161/cib.2.3.8073
Abstract | PDF

The delivery of active molecules into cells requires the efficient translocation of the plasma membrane barrier. Penetratin is a promising cell penetrating peptide is which crosses the cell membrane by a receptor and metabolic energy-independent mechanism. In previous work, we have shown that basic peptides induce membrane invaginations (i.e., tubes formation by induction of negative curvature of membranes) suggesting a new mechanism for cellular uptake of cell penetrating peptides: “physical endocytosis”. These effects on membrane curvature are favored in pure liquid disordered but not in pure liquid ordered (raft-like) membrane domains. Herein, we present experiments in heterogeneous membranes composed of mixed domains. The results show that Penetratin is able to induce invaginations in membranes in which liquid ordered and liquid disordered membranes coexist. We suggest that Penetratin is able to recruit specific lipids locally forming fluid membrane patches dispersed inside a liquid ordered membrane zone resulting in the invagination of tubes composed of heterogeneous membrane domains.


Open Access Article

Mitsugumin 53 (MG53) facilitates vesicle trafficking in striated muscle to contribute to cell membrane repair

Noah Weisleder, Hiroshi Takeshima and Jianjie Ma
Pages 225 - 226
http://dx.doi.org/10.4161/cib.2.3.8077
Abstract | PDF

Repair of the plasma membrane following damage is an important aspect of normal cellular physiology, and disruption of this process is observed in many pathologic states. In a recent series of publications, we resolved that Mitsugumin 53 (MG53) is a novel, muscle-specific member of the tripartite motif/RING B-box Coiled Coil (TRIM/RBCC) family of proteins (TRIM72) that contributes to vesicle trafficking in the course of normal cellular physiology. MG53 can bind phosphatidylserine (PS) with some specificity, and interacts with caveolin-3 (Cav-3) as part of its function in vesicle trafficking.  As part of the response to membrane damage in muscle cells, MG53 acts in an oxidation-dependent manner to facilitate vesicle translocation to the sites of membrane injury where these vesicles are involved in patching the membrane. Here we discuss these findings and examine the implications of this work in the field of membrane repair. Further discussion is provided about potential therapeutic applications for MG53.

Addendum to: Cai C, Masumiya H, Weisleder N, Matsuda N, Nishi M, Hwang M, Ko JK, Lin P, Thornton A, Zhao X, Pan Z, Komazaki S, Brotto M, Takeshima H, Ma J. MG53 nucleates assembly of cell membrane repair machinery. Nat Cell Biol 2009; 11:56–64; PMID: 19043407; DOI: 10.1038/ncb1812.

Cai C, Masumiya H, Weisleder N, Pan Z, Nishi M, Komazaki S, Takeshima H, Ma J. MG53 regulates membrane budding and exocytosis in muscle cells. J Biol Chem 2009; 284:3314–22; PMID: 19029292; doi:10.1074/jbc.M808866200.
and

Masumiya H, Asaumi Y, Nishi M, Minamisawa S, Adachi-Akahane S, Yoshida M, Kangawa K, Ito K, Kagaya Y, Yanagisawa T, Yamazaki T, Ma J, Takeshima H. Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes. Channels 2009; In press.

Open Access Article

The fifth element in animal Gα protein evolution

Yuichiro Oka and Sigrun I. Korsching
Pages 227 - 229
http://dx.doi.org/10.4161/cib.2.3.8080
Abstract | PDF

Heterotrimeric G proteins are key molecules regulating cellular responses to extracellular stimuli, and are composed of α, β and γ subunits. All α subunits in vertebrates belong to four major classes, Gs, Gi, Gq and G12, which are conserved throughout the animal kingdom. Unexpectedly, now a fifth class of Gα protein, Gv, has been discovered. Gv is conserved across the animal kingdom and present in vertebrates, arthropods, mollusks, annelids, and even sponges. Presumably, Gv has been missed so far, because it has been lost in many lineages in the major model organisms such as nematodes, fruit fly, and mammals. On the other hand, gene gains are also observed for Gv, with at least two independent gene duplications, one in sponges and the other in the teleost lineage. Such frequent gene gains and losses fit to a birth-and-death mode of evolution, which is unusual for a well-conserved and ancient gene family like the Gα proteins. The discovery of a novel major class of Gα proteins provides new insights in the evolution of the Gα protein family and opens new possibilities in G protein signaling research.

Open Access Article

Contributions of iridescence to floral patterning

Heather Whitney, Mathias Kolle, Ruben Alvarez-Fernandez, Ullrich Steiner and Beverley Glover
Pages 230 - 232
http://dx.doi.org/10.4161/cib.2.3.8084
Abstract | PDF

The Hibiscus trionum flower is distinctly patterned, with white petals each with a patch of red pigment at the base, producing a ‘bulls-eye’ pattern on the whole flower. The red pigmented patches are also iridescent, due to the presence of a series of overlying cuticular striations that act as a diffraction grating. We have previously reported that scanning electron microscopy revealed a sharply defined difference between the surface structure overlying the pigmented patch and that over the rest of the petal, with the diffraction grating only present over the pigmented region. Here we show that differences in petal surface structure overlie differences in pigment color in three other species, in a range of different patterns. Floral patterns have previously been shown to be advantageous in pollinator attraction, and we discuss whether emphasis of pigment patterns by structural color may increase floral recognition by pollinators.

Open Access Article

The cell wall and endoplasmic reticulum stress responses are coordinately regulated in Saccharomyces cerevisiae

Damian Krysan
Pages 233 - 235
http://dx.doi.org/10.4161/cib.2.3.8097
Abstract | PDF

The unfolded protein response (UPR) is an intracellular signaling pathway that regulates the cellular response to the accumulation of misfolded proteins in eukaryotes. Our group has demonstrated that cell wall stress activates UPR in yeast through signals transmitted by the cell wall integrity (CWI) mitogen-activated protein (MAP) kinase cascade. The UPR is required to maintain cell wall integrity; mutants lacking a functional UPR have defects in cell wall biosynthesis and are hypersensitive to cell wall-directed antifungal drugs.  Since ER stress also activates CWI signaling, we propose that ER and cell wall stress responses are coordinated by CWI and UPR signaling pathways in order to protect cells against these related stressors.  Further investigation of the mechanisms of this coordinate regulation may lead to improved cell wall-directed antifungal therapies.

Open Access Article

Tough times call for bigger brains

Timothy Roth and Vladimir Pravosudov
Pages 236 - 238
http://dx.doi.org/10.4161/cib.2.3.8099
Abstract | PDF

Memory is crucial for survival in many animals. Spatial memory in particular is important for food-caching species and may be influenced by selective pressures such as climate. The influence of climate on memory may be facilitated through the hippocampus (Hp), the part of the brain responsible in part for spatial memory. In a recent paper, we conducted the first large-scale test of the relationship between memory, the climate, and the brain in a single food-caching species, the black-capped chickadee (Poecile atricapillus). We found that birds from more harsh northern climates had significantly larger hippocampal volumes and more neurons than those from more mild southern latitudes.  This work suggests that environmental pressures are capable of influencing specific brain regions, which may result in enhanced memory, and hence survival, in harsh climates. This work gives us a better understanding of how the brain responds to different environments and how animals can adapt to their environment in general.

Open Access Article

Connexin 43 hemichannel opening associated with Prostaglandin E₂ release is adaptively regulated by mechanical stimulation

Sirisha Burra and Jean X. Jiang
Pages 239 - 240
http://dx.doi.org/10.4161/cib.2.3.8154
Abstract | PDF

Osteocytes present in the bone are known to be the major mechanosensory cells. Their involvement in mechanoregulation of bone remodeling is not yet clear. Osteocytes are connected with each other thorough gap junctions formed by Connexin 43 (Cx43). Apart from forming gap junctions; Cx43 in osteocytes is also present in the form of hemichannels. Recently, we have developed a unique antibody that specifically blocks hemichannels and does not have any effect on gap junctions. Cx43 hemichannels present in osteocytes of the bone are mechanosensory in nature as they open when subjected to mechanical stimulation in the form of fluid flow shear stress (FFSS). Opening of Cx43 hemichannels results in the release of molecules like PGE2 that are involved in bone remodeling. Our recent report shows that the opening of Cx43 hemichannels depends on the magnitude and duration of shear stress. When osteocytes are subjected to FFSS followed by a brief incubation and reapplication of FFSS, it led to further increase in opening of Cx43 hemichannels. Application of continuous FFSS for longer periods of time (24 hrs) results in decreased opening of hemichannels. These results show that Cx43 hemichannels are adaptive in response to mechanical stimulation, possibly to regulate the release PGE2 during bone remodeling.

Open Access Article

Ion channels as effectors in carbon monoxide signaling

Chris Peers, Mark L. Dallas and Jason L. Scragg
Pages 241 - 242
http://dx.doi.org/10.4161/cib.2.3.8158
Abstract | PDF

A wealth of recent studies has highlighted the diverse and important influences of carbon monoxide (CO) on cellular signaling pathways. Such studies have implicated CO, and the enzymes from which it is derived (heme oxygenases) as potential therapeutic targets, particularly (although not exclusively) in inflammation, immunity and cardiovascular disease.¹ In a recent study,² we demonstrated that CO inhibited cardiac L-type Ca2+ channels. This effect arose due to the ability of CO to bind to mitochondria (presumably at complex IV of the electron transport chain) and so cause electron leak which resulted in increased production of reactive oxygen species. These modulated the channel’s activity through interactions with three cysteine residues in the cytosolic C-terminus of the channel’s major, pore-forming subunit. Our study provided a potential mechanism for the cardioprotective effects of CO and also highlighted ion channels as a major potential target group for this gasotransmitter.

Open Access Article

Tunneling nanotubes (TNT): a potential mechanism for intercellular trafficking

Eliseo A. Eugenin, Peter J. Gaskill and Joan W. Berman
Pages 243 - 244
http://dx.doi.org/10.4161/cib.2.3.8165
Abstract | PDF

Cell-to-cell communication coordinates the development of multicellular systems, and is mediated by soluble factors, gap junctions and the recently described tunneling nanotubes (TNT).  Both TNT and gap junctions facilitate the transfer of intracellular mediators between the cytoplasm of connected cells. We recently described that HIV induced the formation of TNT in human primary macrophages in correlation with viral replication. Based on these results we hypothesized that during HIV infection, TNTs are hijacked by HIV to spread infection. TNT like structures may be a novel mechanism of amplification of HIV infection. Our findings and those of others require further investigation to identify the specific mechanims by which pathogens use TNT.




REVIEW

Open Access Article

Identification and bioinformatics characterization of translation initiation complex eIF4F components and poly(A)-binding protein from Plasmodium falciparum

Renu Tuteja
Pages 245 - 260
http://dx.doi.org/10.4161/cib.2.3.8843
Abstract | PDF

Protein synthesis in eukaryotes initiates with binding of the multisubunit translation initiation complex eIF4F.  This complex contains eIF4E, eIF4A and eIF4G.  eIF4E directly interacts with the cap structure, eIF4A is an RNA helicase and eIF4G acts as a scaffold for the complex.  eIF4G contains the binding sites for both the subunits i.e. eIF4A and eIF4E and it also interacts with poly(A)-binding protein (PABP).  In present study we have identified and characterized the main components of the eIF4F complex i.e. eIF4E, eIF4A and eIF4G and PABP from Plasmodium falciparum.  Molecular modeling of PfeIF4E, PfeIF4G and PfPABP confirms that they contain all the characteristic conserved structural features.  We have annotated some of the genes of P. falciparum and as a result these studies demonstrate that the components of translation initiation complex are highly conserved.  Therefore these studies will contribute to understand the basic biology and components of translation complex in P. falciparum.




MINI-REVIEWS

Open Access Article

Neuregulin links dopaminergic and glutamatergic neurotransmission to control hippocampal synaptic plasticity

Joerg Neddens, Detlef Vullhorst and Andres Buonanno
Pages 261 - 264
http://dx.doi.org/10.4161/cib.2.3.7825
Abstract | PDF

Neuregulin-1 (NRG-1) and its receptor ErbB4 are genetically linked with schizophrenia, a complex developmental disorder of high heritability but unknown etiology that has been proposed to result from deficits in functional connectivity and synaptic plasticity. Based on pharmacological evidence, disbalances in dopaminergic and glutamatergic transmission systems are believed to contribute to its pathophysiology, but genetic data supporting a causative role for either are sparse. Stimulation of NRG-1/ErbB4 signaling inhibits or reverts hippocampal long-term potentiation at glutamatergic synapses between Schaeffer collateral afferents and CA1 pyramidal neurons (SC->CA1). We have recently demonstrated that NRG-1 regulates glutamatergic plasticity by rapidly increasing extracellular hippocampal dopamine levels and activation of D4 dopamine receptors (D4R). These new findings position NRG-1/ErbB4 signaling pathway at the crossroads between dopaminergic and glutamatergic neurotransmission and offer novel ways to consolidate genetic, functional and pharmacological data toward a better understanding of the etiological processes underlying schizophrenia, and the role of NRG-1 for normal synaptic function and plasticity. The currently available data suggest that hippocampal interneurons might play a crucial role in mediating NRG-1 induced depotentiation. This interpretation is in line with other evidence pointing towards an involvement of GABAergic cells in the etiology of schizophrenia.

Open Access Article

Brain activation and the locus of visual awareness

Konstantinos Moutoussis
Pages 265 - 267
http://dx.doi.org/10.4161/cib.2.3.8039
Abstract | PDF

A major problem in visual neuroscience is to distinguish neuronal activity which is directly related to the conscious percept. The word “directly” is used here as opposed to an indirect relationship, as is for example the case with activity in the retina, which is produced by a stimulus in the outside world and will eventually lead to the perception of this stimulus. As for the word “related”, it is used to mean activity which creates the perceptual experience or, even more extremely, activity that is the perceptual experience. The distinction between the two (is vs. creates) is not straightforward, although there might be some differences between them. Philosophers would argue that they have a different phenomenology, the percept existing only for the perceiving person, whereas the underlying neuronal activation exists for all to observe. One could go on to argue that it is actually not the neuronal activation that “everybody” observes, but each one observes his own percept of it, which is also unique and subjective. Still, the content of this percept and the one of the original stimulus are quite different. The purpose of the present review is not to dig deep into such philosophical issues, but rather to give an overview of neuroscientific approaches trying to locate the neural correlate of conscious perception.

Open Access Article

Role of drebrin A in dendritic spine plasticity and synaptic function: implications in neurological disorders

Anton Ivanov, Monique Esclapez and Lotfi Ferhat
Pages 268 - 270
http://dx.doi.org/10.4161/cib.2.3.8166
Abstract | PDF

Drebrin A is one of the most abundant neuron-specific binding proteins of F-actin and its expression is increased in parallel with synapse formation. Drebrin A is particularly concentrated in dendritic spines, postsynaptic sides of excitatory glutamatergic synapses. More recently, Ferhat and colleagues reported the functional role of drebrin A in regulating synaptic transmission. Indeed, our study showed that overexpression of drebrin A induced an increase of glutamatergic but not GABAergic synapses and resulted in the alteration of the normal excitatory-inhibitory ratio in favour of excitation in mature hippocampal neurons. Downregulation of drebrin A expression by antisense oligonucleotides resulted in the decrease of both miniature- glutamatergic and GABAergic synaptic activities without affecting the excitatory-inhibitory ratio. Studies performed in heterologous cells revealed that drebrin A reorganized the actin filaments and stabilized them and that these effects are depend upon its actin-binding domain. These results suggest that drebrin A regulates dendritic spine morphology, size and density, presumably via regulation of actin cytoskeleton remodeling and dynamics. These data demonstrate for the first time that an actin-binding protein such as drebrin A regulates both glutamatergic and GABAergic synaptic transmissions, probably through an increase of active synaptic site density for glutamatergic transmission and through homeostatic mechanisms for the GABAergic one.

Open Access Article

Mouse models to investigate the function of spermine

Anthony E. Pegg and Xiaojing Wang
Pages 271 - 274
http://dx.doi.org/10.4161/cib.2.3.8225
Abstract | PDF

Many functions have been ascribed to polyamines, but there has been no clear identification of a unique role for spermine. The Gy mouse has a deletion of part of the X chromosome that includes the SMS gene encoding spermine synthase. Tissues from male Gy mice have no spermine but increased spermidine. They have multiple abnormalities including a tendency to sudden death, small size, circling behavior and other neurological symptoms, sterility and deafness. These changes are reversed by breeding with mice expressing a spermine synthase transgene. Detailed studies of hearing in Gy mice show that the absence of spermine synthase leads to loss of the endocochlear potential. Since this potential requires the cochlear lateral wall-specific Kir4.1 channel, regulation by spermine of transport via these channels appears to be an essential function. A similar spermine-related defect in the functioning of cardiac Kir channels could account for arrhythmias leading to sudden death. The effect of the absence of spermine on glutamate receptor ion channels in the brain may account for the neurological symptoms and could contribute to the lack of fertility and normal growth but more direct effects on gene expression are also possible. Advantages and limitations of the Gy model are discussed.

Open Access Article

Environmental stresses and clinical drugs paralyze a cell

Yukifumi Uesono
Pages 275 - 278
http://dx.doi.org/10.4161/cib.2.3.8226
Abstract | PDF

Cells respond and adapt to various extracellular changes. Environmental stresses, such as high osmolarity and acute glucose deprivation, rapidly and transiently shut down translation initiation and actin polarization in the yeast Saccharomyces cerevisiae.  Certain clinical drugs, such as local anesthetics and antipsychotic phenothiazines, and cationic surfactants also cause shutdowns similar to those triggered by environmental stresses. These compounds all have an amphiphilic structure, a cationic hydrophilic region, surfactant activity, and the ability to lyse yeast cells. Since low concentrations of these compounds shut down intracellular reactions in the absence of cell lysis, the compounds might change the state of the cell’s membrane by intercalating into the membrane and thus generate signals for the shutdown, as do environmental stresses. The intracellular shutdowns caused by stresses might essentially be the same as the paralysis caused by clinical drugs at the cellular level.

Open Access Article

Chemical communication and mother-infant recognition

Stefano Vaglio
Pages 279 - 281
http://dx.doi.org/10.4161/cib.2.3.8227
Abstract | PDF

Fifty years after the term ‘pheromone’ was coined by Peter Karlson and Martin Lüsher, the search for these semiochemicals is still an elusive goal of chemical ecology and communication studies. Contrary to what appears in the popular press, the race is still on to capture and define human scents. Over the last several years, it became increasingly clear that pheromone-like chemical signals probably play a role in offspring identification and mother recognition. Recently, we analyzed the volatile compounds in sweat patch samples collected from the para-axillary and nipple-areola regions of women during pregnancy and after childbirth. We hypothesized that, at the time of birth and during the first weeks of life, the distinctive olfactory pattern of the para-axillary area is probably useful to newborns for recognizing and distinguishing their own mother, whereas the characteristic pattern of the nipple-areola region is probably useful as a guide to nourishment.

Open Access Article

Audience effects in chimpanzee copulation calls

Simon W. Townsend and Klaus Zuberbuhler
Pages 282 - 284
http://dx.doi.org/10.4161/cib.2.3.6796
Abstract | PDF

Audience effects arise when the signaling behavior of animals is affected by the presence of others. Whilst this phenomenon has been documented in numerous animal species, very little research has addressed what effect the listening audience has in the mating context. In this article we discuss our recent findings that the production of chimpanzee copulation calls is effected by the presence of potentially eavesdropping females and males. We relate these results to understanding the function of primate copulation calls in addition to what more they can tell us about the cognitive processes underlying primate call production.




OPINION ARTICLE

Open Access Article

Why are bystanders friendly to recipients of aggression?

Orlaith N. Fraser, Sonja E. Koski, Roman M. Wittig and Filippo Aureli
Pages 285 - 291
http://dx.doi.org/10.4161/cib.2.3.8718
Abstract | PDF

The escalation of conflicts of interest into aggressive conflict can be costly in terms of increased post-conflict stress and damage to the opponents’ relationship. Some costs may be mitigated through post-conflict interactions. One such type of interaction is affiliative contact from a bystander to the recipient of aggression. This type of interaction has been suggested to have a number of functions, including stress reduction and opponent relationship repair. It may also protect bystanders from redirected aggression from the original recipient of aggression. Here we review the evidence for such functions and propose a framework within which the function and occurrence of post-conflict affiliation directed from a bystander to the recipient of aggression is related to the quality of the relationships between the individuals involved and the patterns of behavior expressed.