How do inositol phosphates regulate calcium signaling?

Activation of a variety of cell surface receptors results in the phospholipase C-catalyzed hydrolysis of the minor plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate, with concomitant formation of inositol 1,4,5-trisphosphate and diacylglycerol. There is strong evidence that inositol 1,4,5-trisphosphate stimulates Ca2+ release from intracellular stores. The Ca2+-releasing actions of inositol 1,4,5-trisphosphate are terminated by its metabolism through two distinct pathways. Inositol 1,4,5-trisphosphate is dephosphorylated by a 5-phosphatase to inositol 1,4-bisphosphate; alternatively, inositol 1,4,5-trisphosphate can also be phosphorylated to inositol 1,3,4,5-tetrakisphosphate by a 3-kinase. Although the mechanism of Ca2+ mobilization is understood, the precise mechanisms involved in Ca2+ entry are not known; the proposal that inositol 1,4,5-trisphosphate secondarily elicits Ca2+ entry by emptying an intracellular Ca2+ pool is considered.     

Do caveolins regulate cells by actions outside of caveolae?

Caveolae (caveolin-containing lipid rafts) are plasma membrane domains that scaffold and organize a variety of important proteins in eukaryotic cells. Recent work shows that caveolins can act independently of caveolae, both in cells that lack caveolae (e.g. neurons and leukocytes) and in non-caveolar regions of cells that have caveolae (e.g. cardiac myocytes and fibroblasts). Phosphorylation of caveolins can influence the scaffolding of protein partners, and caveolins appear to participate in the protection and trafficking of proteins to and from the plasma membrane. Together, these results suggest that, despite their name, caveolins should now be thought of as proteins that scaffold signaling and other proteins in both caveolar and non-caveolar regions.     

Cell-to-cell signaling through light: just a ghost of chance?

Despite the large number of reports attributing the signaling between detached cell cultures to the electromagnetic phenomena, almost no report so far included a rigorous analysis of the possibility of such signaling.In this paper, we examine the physical feasibility of the electromagnetic communication between cells, especially through light, with regard to the ambient noise illumination. We compare theoretically attainable parameters of communication with experimentally obtained data of the photon emission from cells without a specially pronounced ability of bioluminescence.We show that the weak intensity of the emission together with an unfavorable signal-to-noise ratio, which is typical for natural conditions, represent an important obstacle to the signal detection by cells.     

Grassland-herbivore interactions: how do grazers coexist?

We develop a new approach to modeling grazing systems that links foraging characteristics (intake and digestive constraints) with resource dynamics via the probability of encounter with different grass heights. Three complementary models are presented: the generation of a grass height structure through selective grazing; investigating the conditions for consumer coexistence; and, using a simplified resource structure, the consequences for consumer abundance. The main finding is that coexistence between grazers differing in body size is possible if a single-resource type becomes differentiated in its height structure. Large grazers can facilitate food availability for smaller species but with the latter being competitively dominant. The relative preference given to different resource partitions is important in determining the nature of population interactions. Large-body and small-body grazer populations can interact through competitive, parasitic, commensalist, or amensalist relationships, depending on the way they partition the resource as well as their relative populations and the dynamics of resource renewal. The models provide new concepts of multispecies carrying capacity (stock equilibrium) in grazed systems with implications for conservation and management. We conclude that consumer species are not substitutable; therefore, the use of rangeland management concepts such as "livestock units" may be inappropriate.     

Anterograde transport through the Golgi complex: do Golgi tubules hold the key?

Biochemical studies have suggested that anterograde protein transport through the Golgi complex is mediated by coatomer-coated vesicles that bud from one compartment and then transfer to, and fuse with, the next. However, recent genetic studies have shown that coatomer mutations block retrograde, but not anterograde, transport in yeast, calling into question the role of coatomer vesicles in anterograde transport. Peggy Weidman proposes that these findings might be explained if anterograde transport occurs by transient fusion of Golgi tubules and if coatomers have related, but separable, functions in tubule and vesicle dynamics.     

Modulation of PP2A activity by Jacalin: is it through caveolae and ER chaperones?

Plant lectins have been reported to affect the proliferation of different human cancer cell line probably by binding to the specific carbohydrate moieties. In the present study, Badan labeled single cysteine mutant (present in the caveolin-1 binding motif) of jacalin (rJacalin) was found to penetrate the target membrane, indicating a protein-protein or protein-membrane interaction apart from its primary mode of binding i.e. protein-carbohydrate interaction. Further, Jacalin treatment has resulted in the movement of the GFP-Caveolin-1 predominantly at the cell-cell contact region with much restricted dynamics. Jacalin treatment has resulted in the perinuclear accumulation of PP2A and dissociation of the PHAP1/PP2A complex. PP2A was found to act as a negative regulator of ERK signaling and a significant decrease in the phosphorylation level of MEK and AKT (T308) in A431. In addition, we have also identified several ER resident proteins including molecular chaperones like ORP150, Hsp70, Grp78, BiP of A431 cells, which were bound to the Jacalin-sepharose column. Among various ER chaperones that were identified, ORP150 was found to present on the cell surface of A431 cells.     

Evolution of intra‐ejaculate sperm interactions: do sperm cooperate?

Sperm are often considered to be individuals, in part because of their unique genetic identities produced as a result of synapsis during meiosis, and in part due to their unique ecology, being ejected away from the soma to continue their existence in a foreign environment. Selection at the level of individual sperm has been suggested to explain the evolution of two enigmatic sperm phenotypes: sperm heteromorphism, where more than one type of sperm is produced by a male, and sperm conjugation, where multiple sperm join together for motility and transport through the female reproductive tract before dissociation prior to fertilization. In sperm heteromorphic species, only one of the sperm morphs typically participates in fertilization, with the non‐fertilizing “parasperm” being interpreted as reproductive altruists. Likewise, in species with sperm conjugation, high levels of sperm mortality have been suggested to be required for conjugate break‐up and this has been considered evidence of kin‐selected altruism. However, it is unclear if sperm possess the heritable variation in fitness (i.e. are individuals) required for the evolution of cooperation. We investigate the question of sperm individuality by focusing on how sperm morphology is determined and how sperm conjugates are formed. Concentrating on sperm conjugation, we discuss functional hypotheses for the evolutionary maintenance of this remarkable trait. Additionally, we speculate on the potential origins of sperm heteromorphism and conjugation, and explore the diversification and losses of these traits once they have arisen in a lineage. We find current evidence insufficient to support the concept of sperm control over their form or function. Thus, without additional evidence of haploid selection (i.e. sperm phenotypes that reflect their haploid genome and result in heritable differences in fitness), sperm heteromorphism and conjugation should be interpreted not as cooperation but rather as traits selected at the level of the male, much like other ejaculatory traits such as accessory gland proteins and ejaculate size.     

Intracellular signaling pathways activated by kisspeptins through GPR54: do multiple signals underlie function diversity?

Kisspeptins, a family of peptide products derived from the KiSS-1 gene, activate their cognate receptor GPR54 in various target tissues to exert disparate functions, including inhibition of tumor metastasis and control of reproductive function. In contrast to the plethora of studies that have analyzed in recent years the regulatory functions of the KiSS-1/GPR54 system, only a limited number of reports have been primarily focused on delineating the intracellular signaling pathways involved. Nevertheless, there is solid evidence indicating that kisspeptin can activate a wide variety of signals via GPR54. These include typical G-protein (Galphaq/11)-coupled cascades, such as activation of phospholipase C (PLC), and subsequent accumulation of inositol-(1,4,5)-triphosphate (IP3), intracellular Ca(2+) mobilization, and activation of protein kinase C. However, kisspeptin also activates pathways related to mitogen activated protein kinases (MAPK), especially ERK1/2, and p38 and phosphatidylinositol-3-kinase (PI3K)/Akt. Additionally, the kisspeptin/GPR54 pair can also influence cell signaling by interacting with other receptors, such as chemokine receptor CXCR4, and GnRH receptor. Kisspeptin can also affect other signaling events, like expression of matrix metalloproteinase 9 (via NFkappaB), and that of calcineurin. The information gathered hitherto clearly indicates that activation of a specific set of interconnected signals is selectively triggered by kisspeptin via GPR54 in a cell type-dependent manner to precisely regulate functions as distinct as hormone release and cell migration. In this scenario, it will be important to decipher kisspeptin/GPR54 signaling mechanisms in reproductive and non-reproductive tissues by studying additional models, especially on natural kisspeptin targets expressing endogenous GPR54.     

How do plants regulate the function, community structure, and diversity of mycorrhizal fungi?

In many semi-natural and natural ecosystems, mycorrhizal fungi are the most abundant and functionally important group of soil micro-organisms. They are almost wholly dependent on their host plants to supply them with photosynthate in return for which they enable the plant to access greater quantities of nutrients. Thus, there is considerable potential for plant communities to regulate the structure and function of mycorrhizal communities. This paper reviews some of the key recent developments that have enabled the influence of plant species richness, composition, and age on mycorrhizal communities in boreal forests and temperate grassland to be determined. It discusses the emerging evidence that, in some situations, plant species richness is related to mycorrhizal species richness, in contrast to previous thinking. The paper also includes some preliminary data on the effect of host stand age on root-associated basidiomycete communities. It concludes by highlighting some of the new methodological advances that promise to unravel the linkages between mycorrhizal diversity and their function in situ.     

Direct targeting of β-catenin: Inhibition of protein–protein interactions for the inactivation of Wnt signaling

The activation of developmental signaling pathways such as Notch, Hedgehog and Wnt has implications in the onset and progression of numerous types of cancer. Consequently, targeting of such pathways is considered an attractive therapeutic approach. Inhibition of the Wnt signaling cascade proves to be complicated, in part, due to the lack of druggable pathway components. The central hub in Wnt signaling is the protein β-catenin, which is involved in numerous protein–protein interactions. In general, the inhibition of protein–protein interactions is challenging in particular with binding interfaces lacking pronounced hydrophobic pockets. Herein, we give an overview of β-catenin–protein interactions, and we review active agents that were reported to inhibit canonical Wnt signaling via direct targeting of β-catenin.     

Periodontal ligament-associated protein-1 knockout mice regulate the differentiation of osteoclasts and osteoblasts through TGF-β1/Smad signaling pathway

It has been known that periodontal ligament-associated protein-1 (PLAP-1/Asporin) not only inhibits cartilage formation in osteoarthritis, but it also influences the healing of skull defect. However, the effect and mechanism of PLAP-1/Asporin on the mutual regulation of osteoclasts and osteoblasts in periodontitis are not clear. In this study, we utilized a PLAP-1/Asporin gene knockout (KO) mouse model to research this unknown issue. We cultured mouse bone marrow mesenchymal stem cells with Porphyromonas gingivalis lipopolysaccharide (P.g. LPS) for osteogenic induction in vitro. The molecular mechanism of PLAP-1/Asporin in the regulation of osteoblasts was detected by immunoprecipitation, immunofluorescence, and inhibitors of signaling pathways. The results showed that the KO of PLAP-1/Asporin promoted osteogenic differentiation through transforming growth factor beta 1 (TGF-β1)/Smad3 in inflammatory environments. We further found the KO of PLAP-1/Asporin inhibited osteoclast differentiation and promoted osteogenic differentiation through the TGF-β1/Smad signaling pathway in an inflammatory coculture system. The experimental periodontitis model was established by silk ligation and the alveolar bone formation in PLAP-1/Asporin KO mice was promoted through TGF-β1/Smad3 signaling pathway. The subcutaneous osteogenesis model in nude mice also confirmed that the KO of PLAP-1/Asporin promoted bone formation by the histochemical staining. In conclusion, PLAP-1/Asporin regulated the differentiation of osteoclasts and osteoblasts through TGF-β1/Smad signaling pathway. The results of this study lay a theoretical foundation for the further study of the pathological mechanism underlying alveolar bone resorption, and the prevention and treatment of periodontitis.     

Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation?

Many types of cell show different aspects of polarization. Epithelial cells display a ubiquitous apical-basolateral polarity but often are also polarized in the plane of the epithelium - a feature referred to as 'planar cell polarity' (PCP). In Drosophila all adult epithelial cuticular structures are polarized within the plane, whereas in vertebrates examples of PCP include aspects of skin development, features of the inner ear epithelium, and the morphology and behavior of mesenchymal cells undergoing the morphogenetic movement called 'convergent extension'. Recent advances in the study of PCP establishment are beginning to unravel the molecular mechanisms that underlie this aspect of cell and tissue differentiation. Here I discuss new developments in our molecular understanding of PCP in Drosophila and compare them towhat is known about the regulation of convergent extension in vertebrates.     

ROS signaling: the new wave?

Reactive oxygen species (ROS) play a multitude of signaling roles in different organisms from bacteria to mammalian cells. They were initially thought to be toxic byproducts of aerobic metabolism, but have now been acknowledged as central players in the complex signaling network of cells. In this review, we will attempt to address several key questions related to the use of ROS as signaling molecules in cells, including the dynamics and specificity of ROS signaling, networking of ROS with other signaling pathways, ROS signaling within and across different cells, ROS waves and the evolution of the ROS gene network.     

Wnt signaling: the naked truth?

Frizzled receptors can activate two alternative signal transduction pathways: the canonical Wnt pathway or the planar cell polarity pathway. Recent studies of the Naked cuticle protein suggest a mechanism for the inactivation of the canonical pathway and concomitant activation of the planar cell polarity pathway.     

Ectoparasites: are they the proximate cause of cleaning interactions?

We tested the importance of ectoparasites in cleaning symbioses by comparing the activity of Caribbean cleaning gobies ( Elacatinus evelynae ) and of their clients during three daily periods (early morning, midday and late afternoon) in which ectoparasite availability varied naturally. Emergence from the benthos of gnathiid isopod larvae, the main target of cleaning goby predation, was higher at night, when cleaners are inactive, than during the day. Overall ectoparasite loads also tended to be higher on clients in the morning. This coincided with higher rates of visits to cleaning stations by client fish in the morning than at midday, but high rates of client visits were also recorded in the late afternoon. Clients were more likely to adopt stereotypical incitation poses, which increase the likelihood of being cleaned, in the morning than later in the day. Inspection bouts by cleaning gobies were longest in the morning. Cleaner and client behaviours therefore change predictably in response to natural diurnal variation in ectoparasite availability. These results add to a growing number of studies supporting the idea that cleaning symbioses are mutualisms dependent on ectoparasite removal.     

Info-gap robust-satisficing model of foraging behavior: do foragers optimize or satisfice?

In this note we compare two mathematical models of foraging that reflect two competing theories of animal behavior: optimizing and robust satisficing. The optimal-foraging model is based on the marginal value theorem (MVT). The robust-satisficing model developed here is an application of info-gap decision theory. The info-gap robust-satisficing model relates to the same circumstances described by the MVT. We show how these two alternatives translate into specific predictions that at some points are quite disparate. We test these alternative predictions against available data collected in numerous field studies with a large number of species from diverse taxonomic groups. We show that a large majority of studies appear to support the robust-satisficing model and reject the optimal-foraging model.     

Unraveling interactions: do temperature and competition with native species affect the performance of the non-indigenous sun coral Tubastraea coccinea?

Coral Reefs - The impact of invasive species has been increasing in recent decades due to globalization, threatening marine biodiversity. Tubastraea spp. (sun corals) have been spreading worldwide,...     

Anhydrobiosis: the model worm as a model?

New work now shows that the dauer larvae of Caenorhabditis elegans can survive anhydrobiotically. The genetic tractability of this model organism may be useful in studying how organisms survive when losing most or all of their water.