1,106 research outputs found

    Centrosome-intrinsic mechanisms modulate centrosome integrity during fever

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    The centrosome is critical for cell division, ciliogenesis, membrane trafficking, and immunological synapse function. The immunological synapse is part of the immune response, which is often accompanied by fever/heat stress (HS). Here we provide evidence that HS causes deconstruction of all centrosome substructures primarily through degradation by centrosome-associated proteasomes. This renders the centrosome nonfunctional. Heat-activated degradation is centrosome selective, as other nonmembranous organelles (midbody, kinetochore) and membrane-bounded organelles (mitochondria) remain largely intact. Heat-induced centrosome inactivation was rescued by targeting Hsp70 to the centrosome. In contrast, Hsp70 excluded from the centrosome via targeting to membranes failed to rescue, as did chaperone inactivation. This indicates that there is a balance between degradation and chaperone rescue at the centrosome after HS. This novel mechanism of centrosome regulation during fever contributes to immunological synapse formation. Heat-induced centrosome inactivation is a physiologically relevant event, as centrosomes in leukocytes of febrile patients are disrupted. Cell Biology under license from the author(s)

    Impaired Bone Formation in Transgenic Mice Resulting from Altered Integrin Function in Osteoblasts

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    AbstractTo determine the role of integrins in mature osteoblasts in vivo, we expressed in transgenic mice a dominant-negative integrin subunit (β1-DN) consisting of the β1 subunit cytoplasmic and transmembrane domains, driven by the osteoblast-specific osteocalcin promoter. Immature osteoblasts isolated from transgenic animals differentiated normally in vitro until the osteocalcin promoter became active; thereafter they detached from the substratum, suggesting that β1-DN was impairing adhesion in mature osteoblasts. Transgenic animals had reduced bone mass, with increased cortical porosity in long bones and thinner flat bones in the skull. At 35 days, the rate of bone formation was reduced in cortical bone, and the parietal bones were 45% thinner than in wild-type animals. Active osteoblasts were less polar and had larger areas of cytoplasm with intracellular stores of matrix molecules. Osteocyte lacunae appeared normal around the cell body but did not have normal canilicular structures. At 90 days, the parietal bone of transgenic males was of normal width, suggesting that the original defect in matrix deposition had been repaired or compensated for. In contrast, transgenic females still had decreased bone mass in the parietal bone at 90 days. The decreased bone mass in TG females was accompanied by increased staining for osteoclast activity, suggesting that there was a sex-specific defect in mature animals

    Isolation of the ALG6 locus of Saccharomyces cerevisiae required for glucosylation in the N-linked glycosylation pathway

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    N-Linked protein glycosylation in most eukaryotic cells initiates with the transfer of the oligosaccharide Glc3Man9GlcNAc2 from the lipid carrier dolichyl pyrophosphate to selected asparagine residues. In the yeast Saccharomyces cerevisiae, alg mutations which affect the assembly of the lipid-linked oligosaccharide at the membrane of the endoplasmic reticulum result in the accumulation of lipid-linked oligosaccharide intermediates and a hypoglycosylation of proteins. Exploiting the synthetic growth defect of alg mutations in combination with mutations affecting oligosaccharyl transferase activity (Stagljar et al., 1994), we have isolated the ALG6 locus. alg6 mutants accumulate lipid-linked Man9GlcNAc2, suggesting that this locus encodes an endoplasmic glucosyltransferase. Alg6p has sequence similarity to Alg8p, a protein required for glucosylation of Glc1Man9GlcNAc

    Conserved currents for Kerr and orthogonality of quasinormal modes

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    We introduce a bilinear form for Weyl scalar perturbations of Kerr. The form is symmetric and conserved, and we show that, when combined with a suitable renormalization prescription involving complex r integration contours, quasinormal modes are orthogonal in the bilinear form for different (l, m, n). These properties are apparently not evident consequences of standard properties for the radial and angular solutions to the decoupled Teukolsky relations and rely on the Petrov type D character of Kerr and its t-Ï•\phi reflection isometry. We show that quasinormal mode excitation coefficients are given precisely by the projection with respect to our bilinear form. These properties can make our bilinear form useful to set up a framework for nonlinear quasinormal mode coupling in Kerr. We also provide a general discussion on conserved local currents and their associated local symmetry operators for metric and Weyl perturbations, identifying a collection containing an increasing number of derivatives.Comment: 14+11 pages, 2 figures. minor changes to match version accepted to PR
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