Cell adhesion molecules regulating astrocyte–neuron interactions

A tripartite synapse comprises a neuronal presynaptic axon and a postsynaptic dendrite, which are closely ensheathed by a perisynaptic astrocyte process. Through their structural and functional association with thousands of neuronal synapses, astrocytes regulate synapse formation and function. Recent work revealed a diverse range of cell adhesion–based mechanisms that mediate astrocyte–synapse interactions at tripartite synapses. Here, we will review some of these findings unveiling a highly dynamic bidirectional signaling between astrocytes and synapses, which orchestrates astrocyte morphological maturation and synapse development. Moreover, we will discuss the roles of these newly discovered molecular pathways in brain physiology and function both in health and disease.     

On the role of excitonic interactions in carotenoid–phthalocyanine dyads and implications for photosynthetic regulation

In two recent studies, energy transfer was reported in certain phthalocyanine–carotenoid dyads between the optically forbidden first excited state of carotenoids (Car S₁) and phthalocyanines (Pcs) in the direction Pc → Car S₁ (Kloz et al., J Am Chem Soc 133:7007–7015, 2011) as well as in the direction Car S₁ → Pc (Liao et al., J Phys Chem A 115:4082–4091, 2011). In this article, we show that the extent of this energy transfer in both directions is closely correlated in these dyads. This correlation and the additional observation that Car S₁ is instantaneously populated after Pc excitation provides evidence that in these compounds excitonic interactions can occur. Besides pure energy transfer and electron transfer, this is the third type of tetrapyrrole–carotenoid interaction that has been shown to occur in these model compounds and that has previously been proposed as a photosynthetic regulation mechanism. We discuss the implications of these models for photosynthetic regulation. The findings are also discussed in the context of a model in which both electronic states are disordered and in which the strength of the electronic coupling determines whether energy transfer, excitonic coupling, or electron transfer occurs.

     

Neuron–astrocyte interactions in the medial nucleus of the trapezoid body

The calyx of Held (CoH) synapse serves as a model system to analyze basic mechanisms of synaptic transmission. Astrocyte processes are part of the synaptic structure and contact both pre- and postsynaptic membranes. In the medial nucleus of the trapezoid body (MNTB), midline stimulation evoked a current response that was not mediated by glutamate receptors or glutamate uptake, despite the fact that astrocytes express functional receptors and transporters. However, astrocytes showed spontaneous Ca²⁺ responses and neuronal slow inward currents (nSICs) were recorded in the postsynaptic principal neurons (PPNs) of the MNTB. These currents were correlated with astrocytic Ca²⁺ activity because dialysis of astrocytes with BAPTA abolished nSICs. Moreover, the frequency of these currents was increased when Ca²⁺ responses in astrocytes were elicited. NMDA antagonists selectively blocked nSICs while D-serine degradation significantly reduced NMDA-mediated currents. In contrast to previous studies in the hippocampus, these NMDA-mediated currents were rarely synchronized.     

On the evolution of fish–coral interactions

The biodiversity of tropical reefs is typified by the interaction between fishes and corals. Despite the importance of this ecological association, coevolutionary patterns between these two animal groups have yet to be critically evaluated. After compiling a large dataset on the prevalence of fish–coral interactions, we found that only a minority of fish species associate strongly with live corals (~5%). Furthermore, we reveal an evolutionary decoupling between fish and coral lineage trajectories. While fish lineages expanded in the Miocene, the bulk of coral diversification occurred in the Pliocene/Pleistocene. Most importantly, we found that coral association did not drive major differences in fish diversification. These results suggest that the Miocene fish diversification is more likely related to the development of novel, wave-resistant reef structures and their associated ecological opportunities. Macroevolutionary patterns in reef fishes are thus more strongly correlated with the expansion of reefs than with the corals themselves.     

Systems for the detection and analysis of protein–protein interactions

The analysis of protein–protein interactions is important for developing a better understanding of the functional annotations of proteins that are involved in various biochemical reactions in vivo. The discovery that a protein with an unknown function binds to a protein with a known function could provide a significant clue to the cellular pathway concerning the unknown protein. Therefore, information on protein–protein interactions obtained by the comprehensive analysis of all gene products is available for the construction of interactive networks consisting of individual protein–protein interactions, which, in turn, permit elaborate biological phenomena to be understood. Systems for detecting protein–protein interactions in vitro and in vivo have been developed, and have been modified to compensate for limitations. Using these novel approaches, comprehensive and reliable information on protein–protein interactions can be determined. Systems that permit this to be achieved are described in this review.K. Kuroda, M. Kato and J. Mima contributed equally to this work.     

Habitat complexity modifies ant–parasitoid interactions: implications for community dynamics and the role of disturbance

Species must balance effective competition with avoidance of mortality imposed by predators or parasites to coexist within a local ecological community. Attributes of the habitat in which species interact, such as structural complexity, have the potential to affect how species balance competition and mortality by providing refuge from predators or parasites. Disturbance events such as fire can drastically alter habitat complexity and may be important modifiers of species interactions in communities. This study investigates whether the presence of habitat complexity in the form of leaf litter can alter interactions between the behaviorally dominant host ants Pheidole diversipilosa and Pheidole bicarinata, their respective specialist dipteran parasitoids (Phoridae: Apocephalus sp. 8 and Apocephalus sp. 25) and a single species of ant competitor (Dorymyrmex insanus). We used a factorial design to manipulate competition (presence/absence of competitors), mortality risk (presence/absence of parasitoids) and habitat complexity (presence/absence of leaf litter). Parasitoid presence reduced soldier caste foraging, but refuge from habitat complexity allowed increased soldier foraging in comparison to treatments in which no refuge was available. Variation in soldier foraging behavior correlated strongly with foraging success, a proxy for colony fitness. Habitat complexity allowed both host species to balance competitive success with mortality avoidance. The effect of fire on habitat complexity was also studied, and demonstrated that the immediate negative impact of fire on habitat complexity can persist for multiple years. Our findings indicate that habitat complexity can increase dominant host competitive success even in the presence of parasitoids, which may have consequences for coexistence of subordinate competitors and community diversity in general.     

Subcellular location of astrocytic calcium stores favors extrasynaptic neuron–astrocyte communication

Neuron–astrocyte interactions are important for brain computations and synaptic plasticity. Perisynaptic astrocytic processes (PAPs) contain a high density of transporters that are responsible for neurotransmitter clearance. Metabotropic glutamate receptors are thought to trigger Ca²⁺ release from Ca²⁺ stores in PAPs in response to synaptic activity. Our ultrastructural study revealed that PAPs are actually devoid of Ca²⁺ stores and have a high surface-to-volume ratio favorable for uptake. Astrocytic processes containing Ca²⁺ stores were located further away from the synapses and could therefore respond to changes in ambient glutamate. Thus, the anatomic data do not support communication involving Ca²⁺ stores in tripartite synapses, but rather point to extrasynaptic communication.     

What is the role of astrocyte calcium in neurophysiology?

Astrocytes comprise approximately half of the volume of the adult mammalian brain and are the primary neuronal structural and trophic supportive elements. Astrocytes are organized into distinct nonoverlapping domains and extend elaborate and dense fine processes that interact intimately with synapses and cerebrovasculature. The recognition in the mid 1990s that astrocytes undergo elevations in intracellular calcium concentration following activation of G protein-coupled receptors by synaptically released neurotransmitters demonstrated not only that astrocytes display a form of excitability but also that astrocytes may be active participants in brain information processing. The roles that astrocytic calcium elevations play in neurophysiology and especially in modulation of neuronal activity have been intensely researched in recent years. This review will summarize the current understanding of the function of astrocytic calcium signaling in neurophysiological processes and discuss areas where the role of astrocytes remains controversial and will therefore benefit from further study.     

The role of parent–offspring interactions during and after fledging in the Black-legged Kittiwake

Most bird species endure a high mortality at fledging, and selection should favour parental behaviour diminishing these costs. Post-fledging parental care varies greatly among species and is often linked to parent–offspring recognition. In the Black-legged Kittiwake (Rissa tridactyla), fledglings need to return to the natal nest to be fed by their parents until independence. Rejections of fledglings by non-parent adults may be fairly violent, and parents are expected to recognize and help their chicks at the time of first return. However, previous cross-fostering experiments pointed out that parents are not able to recognize their chicks up to 15 days before fledging. In this paper, we study the behaviour of both parents and juveniles at fledging. We found that parents answered significantly more to their fledgling's calls than to those of others. Compared to silent juveniles, juveniles that called before landing were more likely to be accepted by their parents. No such pattern was observed with foreign juveniles, indicating that fledglings’ voice may carry individual identity. Furthermore, fledglings found their way back to the natal nest faster when parents attended the natal nest and reacted to their offspring's calls than when they were absent or inactive. Such interactions may therefore diminish juvenile mortality at fledging.     

Interactions of neurons with topographic nano cues affect branching morphology mimicking neuron–neuron interactions

We study the effect of topographic nano-cues on neuronal growth-morphology using invertebrate neurons in culture. We use photolithography to fabricate substrates with repeatable line-pattern ridges of nano-scale heights of 10-150?nm. We plate leech neurons atop the patterned-substrates and compare their growth pattern to neurons plated atop non-patterned substrates. The model system allows us the analysis of single neurite-single ridge interactions. The use of high resolution electron microscopy reveals small filopodia processes that attach to the line-pattern ridges. These fine processes, that cannot be detected in light microscopy, add anchoring sites onto the side of the ridges, thus additional physical support. These interactions of the neuronal process dominantly affect the neuronal growth direction. We analyze the response of the entire neuronal branching tree to the patterned substrates and find significant effect on the growth patterns compared to non-patterned substrates. Moreover, interactions with the nano-cues trigger a growth strategy similarly to interactions with other neuronal cells, as reflected in their morphometric parameters. The number of branches and the number of neurites originating from the soma decrease following the interaction demonstrating a tendency to a more simplified neuronal branching tree. The effect of the nano-cues on the neuronal function deserves further investigation and will strengthen our understanding of the interplay between function and form.     

Library-based numerical reduction of the Hodgkin–Huxley neuron for network simulation

We present an efficient library-based numerical method for simulating the Hodgkin–Huxley (HH) neuronal networks. The key components in our numerical method involve (i) a pre-computed high resolution data library which contains typical neuronal trajectories (i.e., the time-courses of membrane potential and gating variables) during the interval of an action potential (spike), thus allowing us to avoid resolving the spikes in detail and to use large numerical time steps for evolving the HH neuron equations; (ii) an algorithm of spike-spike corrections within the groups of strongly coupled neurons to account for spike-spike interactions in a single large time step. By using the library method, we can evolve the HH networks using time steps one order of magnitude larger than the typical time steps used for resolving the trajectories without the library, while achieving comparable resolution in statistical quantifications of the network activity, such as average firing rate, interspike interval distribution, power spectra of voltage traces. Moreover, our large time steps using the library method can break the stability requirement of standard methods (such as Runge–Kutta (RK) methods) for the original dynamics. We compare our library-based method with RK methods, and find that our method can capture very well phase-locked, synchronous, and chaotic dynamics of HH neuronal networks. It is important to point out that, in essence, our library-based HH neuron solver can be viewed as a numerical reduction of the HH neuron to an integrate-and-fire (I&F) neuronal representation that does not sacrifice the gating dynamics (as normally done in the analytical reduction to an I&F neuron).     

Crucial role of the Rcl1p–Bms1p interaction for yeast pre-ribosomal RNA processing

The essential Rcl1p and Bms1p proteins form a complex required for 40S ribosomal subunit maturation. Bms1p is a GTPase and Rcl1p has been proposed to catalyse the endonucleolytic cleavage at site A₂ separating the pre-40S and pre-60S maturation pathways. We determined the 2.0 Å crystal structure of Bms1p associated with Rcl1p. We demonstrate that Rcl1p nuclear import depends on Bms1p and that the two proteins are loaded into pre-ribosomes at a similar stage of the maturation pathway and remain present within pre-ribosomes after cleavage at A₂. Importantly, GTP binding to Bms1p is not required for the import in the nucleus nor for the incorporation of Rcl1p into pre-ribosomes, but is essential for early pre-rRNA processing. We propose that GTP binding to Bms1p and/or GTP hydrolysis may induce conformational rearrangements within the Bms1p-Rcl1p complex allowing the interaction of Rcl1p with its RNA substrate.     

Azospirillum brasilense colonisation of wheat roots and the role of lectin–carbohydrate interactions in bacterial adsorption and root-hair deformation

The dynamics of adsorption of the nitrogen-fixing soil bacteria Azospirillum brasilense 75 and 80 (isolated from soil samples collected in Saratov Oblast, southern Russia) and A. brasilense Sp245 to the roots of seedlings of common spring wheat was studied in relation to inoculum size, period of incubation with the roots and bacterial-growth phase. The number of root-attached cells increased with increasing size of inoculum and time of contact. The saturation of root-surface adsorption was observed by 24 h of co-incubation for A. brasilense 75, by 6 h for A. brasilense 80, and by 3 h for A. brasilense Sp245. The firmness of bacterial–root attachment increased after extended co-incubation. Differences in the adsorption kinetics of the azospirilla were found that were associated with bacterial-growth phases. Azospirilla attached to the roots of their host cultivar more actively than they did to the roots of a non-host cultivar. Adsorption was partially inhibited when the roots were treated with N-acetyl-D-glucosamine. Maximal inhibition occurred after a 3-h exposure of the roots to the bacteria. Root-hair deformation induced with polysaccharide-containing complexes from the Azospirillum capsular material was inhibited by N-acetyl-D-glucosamine and chitotriose, specific haptens of wheat germ agglutinin. A possible mechanism of the mutual influence of bacteria and plants may involve key roles of wheat germ agglutinin, present on the roots, and the polysaccharide-containing components of the Azospirillum capsule.     

Exploring the role of post-translational modifications on protein–protein interactions with survivin

Survivin is a member of the inhibitor of apoptosis protein (IAP) family with crucial roles in apoptosis and cell cycle regulation. Post-translational modifications (PTMs) have a ubiquitous role in the regulation of a diverse range of proteins’ cellular functions and survivin is not an exception. Phosphorylation, acetylation and ubiquitination seem to regulate survivin anti-apoptotic and mitotic roles and also its nuclear localization. In the present review we explore the role of PTMs on protein–protein interactions focused on survivin to provide new insights into the functions and cell localization of this IAP in pathophysiological conditions, which might help the envisioning of novel targeted therapies for diseases characterized by impaired survivin activity. Protein–protein interaction analysis was performed with bioinformatics tools based on published data aiming to give an integrated perspective of this IAP’s role in the cell.