Gareth Griffiths

..An invagination of the membrane, aided by an early cytoskeletal system, may have formed the first cells--initially within primordial vesicles...

..Studies on the protein and lipid composition of model phagosomes containing latex beads are the first step in a systems-biology approach to understanding how these organelles function...

..In the accompanying paper by Kuehnel et al. (doi:10.1242/jcs.034207), more evidence is provided in support of this model from the analysis of actin assembly at the plasma membrane of intact macrophages...

..Live-cell imaging analysis supported the notion that ezrin is necessary for the fusogenic process itself, promoting the transfer of the lysosome content into the phagosomal lumen...

..smegmatis, M. avium and M. tuberculosis H37Rv. Our results argue that both NF-kappaB-dependent and -independent mechanisms are involved in macrophage killing of mycobacteria and that both mechanisms can be enhanced by selected lipids...

..We propose a pathway mediated by sortilin by which selected lysosomal proteins are transported to the phagosome along a Golgi-dependent route during the maturation of phagosomes...

..We argue that the phagosome cAMP-PKA system behaves as a molecular switch that regulates phagosome actin and maturation in macrophages...

..The overall model we present is strongly supported by the data presented in the accompanying paper that focuses on latex bead phagosomes...

..Exosomes released from mycobacteria-infected cells have recently been shown to be pro-inflammatory. A prominent host molecule that is found within these exosomes is Hsp70, a member of the heat-shock family of proteins...

..The time delay between binding and response was on average 2 s...

..Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel...

..smegmatis phagosomes and reduced killing. Thus, the established role of NF-kappaB in the innate immune response can now be expanded to include regulation of membrane trafficking during infection...

..Collectively, our data provide the first characterisation of Rab21 function in early endosome dynamics...

..Thus, we identify IQGAP1 as a novel component involved in the regulation of phagocytosis by mediating the localization of the actin filament nucleator Dia1...

..Our data provide evidence that porins render mycobacteria vulnerable to killing by reactive nitrogen intermediates within phagosomes probably by facilitating uptake of NO across the mycobacterial outer membrane...

..We propose that actin assembled by phagosomes or late endocytic organelles can provide tracks for fusion-partner organelles to move vectorially toward them, via membrane-bound myosins, to facilitate fusion...

..Here, I argue that each phagosome is an individual entity whose behaviour depends on a finite number of stable equilibrium states in its membrane signalling networks...

..The data demonstrate that RanGTP triggers distinct steps of NPC assembly, and suggest a mechanism for the spatial restriction of NPC assembly to the surface of chromatin...

..However, using RNAi ablation, we demonstrate that zyxin is required to recruit Tes, as well as Mena and VASP, but not vinculin or paxillin, to focal adhesions...

..We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties...

..We suggest that the ezrin-dependent actin assembly on the LBP membrane may require active turnover of D4 and D5 PIPs on the organelle membrane...

..Given the space limitation, the fine details necessary to apply these methods have been successfully omitted and will have to be obtained from the technical references we provide...

..Tubular, vesicular and so far not described onion-shaped membranes, which consisted of open membrane sheets, were seen. Thus, the data show that membrane rupture occurs independently of the A17 protein...

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..This approach provides a simple and efficient way of comparing LDs in different compartments. Its utility is illustrated using data from VPARP and LAMP-1 labelling experiments...

..These approaches have led to unique insights directly relevant for the understanding of the biology of intracellular pathogens and the ways by which they subvert their hosts...

..avium. In contrast, the polyunsaturated sigma-3 lipids behaved differently and stimulated pathogen growth. Thus, lipids can be involved in both stimulatory and inhibitory signalling networks in the phagosomal membrane...

..Together with recent data on endosomal dynamics, our results highlight the importance of organelle-specific Rho modulators for actin-dependent organelle organization and dynamics...

..A mathematical model argues that periodic high and low cellular killing activity is more effective than is a continuous process...

..The measured filopodial retraction force-velocity relationship is in agreement with a model for force-dependent multiple motor kinetics...

..The aim of this study was to investigate the association between severe periodontitis and increase in inflammatory and metabolic risk factors for cardiovascular disease...

..This PI(3)P-enriched compartment may be involved in autophagosome biogenesis. Its dynamic relationship with the ER is consistent with the idea that the ER may provide important components for autophagosome formation...

..Collectively, these results provide a molecular foundation for the clinical studies showing a beneficial effect of PC therapy in ulcerative colitis...