957 research outputs found

    Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo

    Get PDF
    Clathrin light chain (CLC) subunits in vertebrates are encoded by paralogous genes CLTA and CLTB, and both gene products are alternatively spliced in neurons. To understand how this CLC diversity influences neuronal clathrin function, we characterized the biophysical properties of clathrin comprising individual CLC variants for correlation with neuronal phenotypes of mice lacking either CLC-encoding gene. CLC splice variants differentially influenced clathrin knee conformation within assemblies, and clathrin with neuronal CLC mixtures was more effective in membrane deformation than clathrin with single neuronal isoforms nCLCa or nCLCb. Correspondingly, electrophysiological recordings revealed that neurons from mice lacking nCLCa or nCLCb were both defective in synaptic vesicle replenishment. Mice with only nCLCb had a reduced synaptic vesicle pool and impaired neurotransmission compared to WT mice, while nCLCa-only mice had increased synaptic vesicle numbers, restoring normal neurotransmission. These findings highlight differences between the CLC isoforms and show that isoform mixing influences tissue-specific clathrin activity in neurons, which requires their functional balance

    Characterizing temporary hydrological regimes at a European scale

    Get PDF
    Monthly duration curves have been constructed from climate data across Europe to help address the relative frequency of ecologically critical low flow stages in temporary rivers, when flow persists only in disconnected pools in the river bed. The hydrological model is 5 based on a partitioning of precipitation to estimate water available for evapotranspiration and plant growth and for residual runoff. The duration curve for monthly flows has then been analysed to give an estimate of bankfull flow based on recurrence interval. The corresponding frequency for pools is then based on the ratio of bank full discharge to pool flow, arguing from observed ratios of cross-sectional areas at flood 10 and low flows to estimate pool flow as 0.1% of bankfull flow, and so estimate the frequency of the pool conditions that constrain survival of river-dwelling arthropods and fish. The methodology has been applied across Europe at 15 km resolution, and can equally be applied under future climatic scenarios

    Initiating head development in mouse embryos: integrating signalling and transcriptional activity

    Get PDF
    The generation of an embryonic body plan is the outcome of inductive interactions between the progenitor tissues that underpin their specification, regionalization and morphogenesis. The intercellular signalling activity driving these processes is deployed in a time- and site-specific manner, and the signal strength must be precisely controlled. Receptor and ligand functions are modulated by secreted antagonists to impose a dynamic pattern of globally controlled and locally graded signals onto the tissues of early post-implantation mouse embryo. In response to the WNT, Nodal and Bone Morphogenetic Protein (BMP) signalling cascades, the embryo acquires its body plan, which manifests as differences in the developmental fate of cells located at different positions in the anterior–posterior body axis. The initial formation of the anterior (head) structures in the mouse embryo is critically dependent on the morphogenetic activity emanating from two signalling centres that are juxtaposed with the progenitor tissues of the head. A common property of these centres is that they are the source of antagonistic factors and the hub of transcriptional activities that negatively modulate the function of WNT, Nodal and BMP signalling cascades. These events generate the scaffold of the embryonic head by the early-somite stage of development. Beyond this, additional tissue interactions continue to support the growth, regionalization, differentiation and morphogenesis required for the elaboration of the structure recognizable as the embryonic head
    • …
    corecore