Neuroligin1: a cell adhesion molecule that recruits PSD-95 and NMDA receptors by distinct mechanisms during synaptogenesis

<p>Abstract</p> <p>Background</p> <p>The cell adhesion molecule pair neuroligin1 (Nlg1) and β-neurexin (β-NRX) is a powerful inducer of postsynaptic differentiation of glutamatergic synapses <it>in vitro</it>. Because Nlg1 induces accumulation of two essential components of the postsynaptic density (PSD) – PSD-95 and NMDA receptors (NMDARs) – and can physically bind PSD-95 and NMDARs at mature synapses, it has been proposed that Nlg1 recruits NMDARs to synapses through its interaction with PSD-95. However, PSD-95 and NMDARs are recruited to nascent synapses independently and it is not known if Nlg1 accumulates at synapses before these PSD proteins. Here, we investigate how a single type of cell adhesion molecule can recruit multiple types of synaptic proteins to new synapses with distinct mechanisms and time courses.</p> <p>Results</p> <p>Nlg1 was present in young cortical neurons in two distinct pools before synaptogenesis, diffuse and clustered. Time-lapse imaging revealed that the diffuse Nlg1 aggregated at, and the clustered Nlg1 moved to, sites of axodendritic contact with a rapid time course. Using a patching assay that artificially induced clusters of Nlg, the time course and mechanisms of recruitment of PSD-95 and NMDARs to those Nlg clusters were characterized. Patching Nlg induced clustering of PSD-95 via a slow palmitoylation-dependent step. In contrast, NMDARs directly associated with clusters of Nlg1 during trafficking. Nlg1 and NMDARs were highly colocalized in dendrites before synaptogenesis and they became enriched with a similar time course at synapses with age. Patching of Nlg1 dramatically decreased the mobility of NMDAR transport packets. Finally, Nlg1 was biochemically associated with NMDAR transport packets, presumably through binding of NMDARs to MAGUK proteins that, in turn, bind Nlg1. This interaction was essential for colocalization and co-transport of Nlg1 with NMDARs.</p> <p>Conclusion</p> <p>Our results suggest that axodendritic contact leads to rapid accumulation of Nlg1, recruitment of NMDARs co-transported with Nlg1 soon thereafter, followed by a slower, independent recruitment of PSD-95 to those nascent synapses.</p

The fully connected N-dimensional skeleton: probing the evolution of the cosmic web

A method to compute the full hierarchy of the critical subsets of a density field is presented. It is based on a watershed technique and uses a probability propagation scheme to improve the quality of the segmentation by circumventing the discreteness of the sampling. It can be applied within spaces of arbitrary dimensions and geometry. This recursive segmentation of space yields, for a $d$-dimensional space, a $d-1$ succession of $n$-dimensional subspaces that fully characterize the topology of the density field. The final 1D manifold of the hierarchy is the fully connected network of the primary critical lines of the field : the skeleton. It corresponds to the subset of lines linking maxima to saddle points, and provides a definition of the filaments that compose the cosmic web as a precise physical object, which makes it possible to compute any of its properties such as its length, curvature, connectivity etc... When the skeleton extraction is applied to initial conditions of cosmological N-body simulations and their present day non linear counterparts, it is shown that the time evolution of the cosmic web, as traced by the skeleton, is well accounted for by the Zel'dovich approximation. Comparing this skeleton to the initial skeleton undergoing the Zel'dovich mapping shows that two effects are competing during the formation of the cosmic web: a general dilation of the larger filaments that is captured by a simple deformation of the skeleton of the initial conditions on the one hand, and the shrinking, fusion and disappearance of the more numerous smaller filaments on the other hand. Other applications of the N dimensional skeleton and its peak patch hierarchy are discussed.Comment: Accepted for publication in MNRA

Fractional Action Cosmology with Power Law Weight Function

Motivated by an earlier work on fractional-action cosmology with a periodic weight function [1], we extend it by choosing a power-law weight function in the action. In this approach, we obtain a varying gravitational coupling constant. We then model dark energy in this paradigm and obtain relevant cosmological parameters.Comment: 12 pages, 9 figures, Contributed talk published in the proceedings of "3rd Italian-Pakistani Workshop on Relativistic Astrophysics

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

The Size Distribution of Void Filaments in a LCDM Cosmology

The size distribution of mini-filaments in voids has been derived from the Millennium Run halo catalogs at redshifts z=0,0.5,1 and 2. It is assumed that the primordial tidal field originated the presence of filamentary substructures in voids and that the void filaments have evolved only little, keeping the initial memory of the primordial tidal field. Applying the filament-finding algorithm based on the minimal spanning tree (MST) technique to the Millennium voids, we identify the mini-filaments running through voids and measure their sizes at each redshift. Then, we calculate the comoving number density of void filaments as a function of their sizes in the logarithmic interval and determine an analytic fitting function for it. It is found that the size distribution of void mini-filaments in the logarithmic interval has an almost universal shape, insensitive to the redshift: In the short-size section it is well approximated as a power-law, while in the long-size section it decreases exponentially. We expect that the universal size distribution of void filaments may provide a useful cosmological probe without resorting to the rms density fluctuations.Comment: MNRAS in press, revised version, two different definitions of void size considered, chi^2 tests of the universality included, more discussions on the universality of the void size distribution adde

Chaotic Friedmann-Robertson-Walker Cosmology

We show that the dynamics of a spatially closed Friedmann - Robertson - Walker Universe conformally coupled to a real, free, massive scalar field, is chaotic, for large enough field amplitudes. We do so by proving that this system is integrable under the adiabatic approximation, but that the corresponding KAM tori break up when non adiabatic terms are considered. This finding is confirmed by numerical evaluation of the Lyapunov exponents associated with the system, among other criteria. Chaos sets strong limitations to our ability to predict the value of the field at the Big Crunch, from its given value at the Big Bang. (Figures available on request)Comment: 28 pages, 11 figure

Inflation and late time acceleration in braneworld cosmological models with varying brane tension

Braneworld models with variable brane tension $\lambda$ introduce a new degree of freedom that allows for evolving gravitational and cosmological constants, the latter being a natural candidate for dark energy. We consider a thermodynamic interpretation of the varying brane tension models, by showing that the field equations with variable $\lambda$ can be interpreted as describing matter creation in a cosmological framework. The particle creation rate is determined by the variation rate of the brane tension, as well as by the brane-bulk energy-matter transfer rate. We investigate the effect of a variable brane tension on the cosmological evolution of the Universe, in the framework of a particular model in which the brane tension is an exponentially dependent function of the scale factor. The resulting cosmology shows the presence of an initial inflationary expansion, followed by a decelerating phase, and by a smooth transition towards a late accelerated de Sitter type expansion. The varying brane tension is also responsible for the generation of the matter in the Universe (reheating period). The physical constraints on the model parameters, resulted from the observational cosmological data, are also investigated.Comment: 25 pages, 8 figures, accepted for publication in European Physical Journal

Reheating the Universe in Braneworld Cosmological Models with bulk-brane energy transfer

The emergence of the cosmological composition (the reheating era) after the inflationary period is analyzed in the framework of the braneworld models, in which our Universe is a three-brane embedded in a five-dimensional bulk, by assuming the possibility of the brane-bulk energy exchange. The inflaton field is assumed to decay into normal matter only, while the dark matter is injected into the brane from the bulk. To describe the reheating process we adopt a phenomenological approach, by describing the decay of the inflaton field by a friction term proportional to the energy density of the field. After the radiation dominated epoch the model reduces to the standard four dimensional cosmological model. The modified field equations are analyzed analytically and numerically in both the extra-dimensions dominate reheating phase (when the quadratic terms in energy density dominate the dynamics), and in the general case. The evolution profiles of the matter, of the scalar field and of the scale factor of the universe are obtained for different values of the parameters of the model, and of the equations of state of the normal and dark matter, respectively. The equation describing the time evolution of the ratio of the energy density of the dark and of the normal matter is also obtained. The ratio depends on the rate of the energy flow between the bulk and the brane. The observational constraint of an approximately constant ratio of the dark and of the baryonic matter requires that the dark matter must be non-relativistic (cold). The model predicts a reheating temperature of the order of $3\times 10^6$ GeV, a brane tension of the order of $10^{25}$ GeV$^4$, and the obtained composition of the universe is consistent with the observational data.Comment: 29 pages, 9 figures, accepted for publication in JCA