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Copper is a cofactor for many cellular enzymes and transporters. It can be loaded onto secreted and endomembrane cuproproteins by translocation from the cytosol into membrane-bound organelles by ATP7A or ATP7B transporters, the genes for which are mutated in the copper imbalance syndromes Menkes disease and Wilson disease, respectively. Endomembrane cuproproteins are thought to incorporate copper stably on transit through the trans-Golgi network, in which ATP7A accumulates by dynamic cycling through early endocytic compartments. Here we show that the pigment-cell-specific cuproenzyme tyrosinase acquires copper only transiently and inefficiently within the trans-Golgi network of mouse melanocytes. To catalyse melanin synthesis, tyrosinase is subsequently reloaded with copper within specialized organelles called melanosomes. Copper is supplied to melanosomes by ATP7A, a cohort of which localizes to melanosomes in a biogenesis of lysosome-related organelles complex-1 (BLOC-1)-dependent manner. These results indicate that cell-type-specific localization of a metal transporter is required to sustain metallation of an endomembrane cuproenzyme, providing a mechanism for exquisite spatial control of metalloenzyme activity. Moreover, because BLOC-1 subunits are mutated in subtypes of the genetic disease Hermansky-Pudlak syndrome, these results also show that defects in copper transporter localization contribute to hypopigmentation, and hence perhaps other systemic defects, in Hermansky-Pudlak syndrome. 相似文献
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Epithelial tissues maintain a robust architecture which is important for their barrier function, but they are also remodelled through the reorganization of cell-cell contacts. Tissue stability requires intercellular adhesion mediated by E-cadherin, in particular its trans-association in homophilic complexes supported by actin filaments through beta- and alpha-catenin. How alpha-catenin dynamic interactions between E-cadherin/beta-catenin and cortical actin control both stability and remodelling of adhesion is unclear. Here we focus on Drosophila homophilic E-cadherin complexes rather than total E-cadherin, including diffusing 'free' E-cadherin, because these complexes are a better proxy for adhesion. We find that E-cadherin complexes partition in very stable microdomains (that is, bona fide adhesive foci which are more stable than remodelling contacts). Furthermore, we find that stability and mobility of these microdomains depend on two actin populations: small, stable actin patches concentrate at homophilic E-cadherin clusters, whereas a rapidly turning over, contractile network constrains their lateral movement by a tethering mechanism. alpha-Catenin controls epithelial architecture mainly through regulation of the mobility of homophilic clusters and it is largely dispensable for their stability. Uncoupling stability and mobility of E-cadherin complexes suggests that stable epithelia may remodel through the regulated mobility of very stable adhesive foci. 相似文献
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Tatiane Lima da Silva Rísia Brígida Gonçalves Cabral Lucas de Assis Silva Andrade Noemia Falcão Nogueira Mariana de Souza Oliveira Ildemar Ferreira 《Journal of Natural History》2018,52(3-4):225-235
Fluvicola nengeta is an insectivorous bird that belongs to the Tyrannidae family, which lives close to bodies of water and can occur in urban areas as well. It makes use of natural and man-made substrates to build its nests. This study aims at describing the reproductive biology of F. nengeta by comparing nests built on vegetation and man-made structures as to their shapes, nest dimensions, building materials, distance from bodies of water and reproductive success. Forty-four nests were found, where 30 were located in vegetation and 14 on man-made structures. Nests did not exhibit any single pattern and were divided into three distinct shapes: closed/globular/base; closed/ovoid/base (45.5%; n = 5 for both) and low cup/base (9%; n = 1). Nests built on man-made structures exhibited a larger amount of anthropic material, such as plastic and paper, instead of plant-derived materials. Nests on man-made structures were found to be higher up from the ground (459.8 ± 46.9 m) and farther from water (232.9 ± 54.8 m) in comparison to those on vegetation (92.2 ± 28.6 m and 7.3 ± 4.7 m, respectively), aside from exhibiting a higher Mayfield reproductive success (37%) when compared to nests built on vegetation (34%). The estimated values of the daily survival rate (DSR) for vegetation nests were 0.997 for the incubation period and 0.928 for the nestling period. In man-made structure nests, DSRs were 0.968 and 0.964, respectively, during the incubation and nestling periods. The period survival rate (PSR) of nests in vegetation was significantly higher than the PSRs of nests in man-made structures during the incubation period. DSRs did not differ between incubation and nestling periods for either nesting sites. 相似文献
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Decisions on ass et allocations are often determined by covariance estimates from historical market data. In this paper, we introduce a wavelet-based portfolio algorithm, distinguishing between newly embedded news and long-run information that has already been fully absorbed by the market. Exploiting the wavelet decomposition into short- and long-run covariance regimes, we introduce an approach to focus on particular covariance components. Using generated data, we demonstrate that short-run covariance regimes comprise the relevant information for periodical portfolio management. In an empirical application to US stocks and other international markets for weekly, monthly, quarterly, and yearly holding periods (and rebalancing), we present evidence that the application of wavelet-based covariance estimates from short-run information outperforms portfolio allocations that are based on covariance estimates from historical data. 相似文献