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61.
62.
The WD repeat protein FAN regulates lysosome size independent from abnormal downregulation/membrane recruitment of protein kinase C 总被引:1,自引:0,他引:1
Möhlig H Mathieu S Thon L Frederiksen MC Ward DM Kaplan J Schütze S Kabelitz D Adam D 《Experimental cell research》2007,313(12):2703-2718
FAN (factor associated with neutral sphingomyelinase [N-SMase] activation) exhibits striking structural homologies to Lyst (lysosomal trafficking regulator), a BEACH protein whose inactivation causes formation of giant lysosomes/Chediak-Higashi syndrome. Here, we show that cells lacking FAN show a statistically significant increase in lysosome size (although less pronounced as Lyst), pointing to previously unrecognized functions of FAN in regulation of the lysosomal compartment. Since FAN regulates activation of N-SMase in complex with receptor for activated C-kinase (RACK)1, a scaffolding protein that recruits and stabilizes activated protein kinase C (PKC) isotypes at cellular membranes, and since an abnormal (calpain-mediated) downregulation/membrane recruitment of PKC has been linked to the defects observed in Lyst-deficient cells, we assessed whether PKC is also of relevance in FAN signaling. Our results demonstrate that activation of PKC is not required for regulation of N-SMase by FAN/RACK1. Conversely, activation of PKC and recruitment/stabilization by RACK1 occurs uniformly in the presence or absence of FAN (and equally, Lyst). Furthermore, regulation of lysosome size by FAN is not coupled to an abnormal downregulation/membrane recruitment of PKC by calpain. Identical results were obtained for Lyst, questioning the previously reported relevance of PKC for formation of giant lysosomes and in Chediak-Higashi syndrome. In summary, FAN mediates activation of N-SMase as well as regulation of lysosome size by signaling pathways that operate independent from activation/membrane recruitment of PKC. 相似文献
63.
64.
Langergraber KE Siedel H Mitani JC Wrangham RW Reynolds V Hunt K Vigilant L 《PloS one》2007,2(10):e973
A large body of theoretical work suggests that analyses of variation at the maternally inherited mitochondrial (mt)DNA and the paternally inherited non-recombining portion of the Y chromosome (NRY) are a potentially powerful way to reveal the differing migratory histories of men and women across human societies. However, the few empirical studies comparing mtDNA and NRY variation and known patterns of sex-biased migration have produced conflicting results. Here we review some methodological reasons for these inconsistencies, and take them into account to provide an unbiased characterization of mtDNA and NRY variation in chimpanzees, one of the few mammalian taxa where males routinely remain in and females typically disperse from their natal groups. We show that patterns of mtDNA and NRY variation are more strongly contrasting in patrilocal chimpanzees compared with patrilocal human societies. The chimpanzee data we present here thus provide a valuable comparative benchmark of the patterns of mtDNA and NRY variation to be expected in a society with extremely female-biased dispersal. 相似文献
65.
Jens G. P. Diller Sophia Drescher Mario Hofmann Max Rabus Heike Feldhaar Christian Laforsch 《Ecology and evolution》2022,12(4)
Invasive alien species are a major threat to ecosystems. Invasive terrestrial plants can produce allelochemicals which suppress native terrestrial biodiversity. However, it is not known if leached allelochemicals from invasive plants growing in riparian zones, such as Impatiens glandulifera, also affect freshwater ecosystems. We used mesocosms and laboratory experiments to test the impact of I. glandulifera on a simplified freshwater food web. Our mesocosm experiments show that leachate from I. glandulifera significantly reduced population growth rate of the water flea Daphnia magna and the green alga Acutodesmus obliquus, both keystone species of lakes and ponds. Laboratory experiments using the main allelochemical released by I. glandulifera, 2‐methoxy‐1,4‐naphthoquinone, revealed negative fitness effects in D. magna and A. obliquus. Our findings show that allelochemicals from I. glandulifera not only reduce biodiversity in terrestrial habitats but also pose a threat to freshwater ecosystems, highlighting the necessity to incorporate cross‐ecosystem effects in the risk assessment of invasive species. 相似文献
66.
Mycobacterium tuberculosis, along with other actinobacteria, harbours proteasomes in addition to members of the general bacterial repertoire of degradation complexes. In analogy to ubiquitination in eukaryotes, substrates are tagged for proteasomal degradation with prokaryotic ubiquitin‐like protein (Pup) that is recognized by the N‐terminal coiled‐coil domain of the ATPase Mpa (also called ARC). Here, we reconstitute the entire mycobacterial proteasome degradation system for pupylated substrates and establish its mechanistic features with respect to substrate recruitment, unfolding and degradation. We show that the Mpa–proteasome complex unfolds and degrades Pup‐tagged proteins and that this activity requires physical interaction of the ATPase with the proteasome. Furthermore, we establish the N‐terminal region of Pup as the structural element required for engagement of pupylated substrates into the Mpa pore. In this process, Mpa pulls on Pup to initiate unfolding of substrate proteins and to drag them toward the proteasome chamber. Unlike the eukaryotic ubiquitin, Pup is not recycled but degraded with the substrate. This assigns a dual function to Pup as both the Mpa recognition element as well as the threading determinant. 相似文献
67.
Introns are generally believed to evolve too rapidly and too erratically to be of much use in phylogenetic reconstructions.
Few phylogenetically informative intron sequences are available, however, to ascertain the validity of this supposition. In
the present study the supposition was tested on the example of the mammalian class II major histocompatibility complex (Mhc) genes of the DRB family. Since the Mhc genes evolve under balancing selection and are believed to recombine or rearrange frequently, the evolution of their introns
could be expected to be particularly rapid and subject to scrambling. Sequences of intron 4 and 5 DRB genes were obtained from polymerase chain reaction-amplified fragments of genomic DNA from representatives of six eutherian
orders—Primates, Scandentia, Chiroptera, Dermoptera, Lagomorpha, and Insectivora. Although short stretches of the introns
have indeed proved to be unalignable, the bulk of the intron sequences from all six orders, spanning >85 million years (my)
of evolution, could be aligned and used in a study of the tempo and mode of intron evolution. The analysis has revealed the
Mhc introns to evolve at a rate similar to that of other genes and of synonymous sites of non-Mhc genes. No evidence of homogenization or large-scale scrambling of the intron sequences could be found. The Mhc introns apparently evolve largely by point mutations and insertions/deletions. The phylogenetic signals contained in the
intron sequences could be used to identify Scandentia as the sister group of Primates, to support the existence of the Archonta
superorder, and to confirm the monophyly of the Chiroptera.
Received: 26 October 1998 / Accepted: 21 December 1998 相似文献
68.
Nishinakamura R Matsumoto Y Matsuda T Ariizumi T Heike T Asashima M Yokota T 《Developmental biology》1999,216(2):481-490
Stat3 is one of the main signaling components of cytokine receptors, including gp130. Here we show that activation of cytokine receptor gp130 resulted in a dramatic ventralization of Xenopus embryos and that the ventralization correlated well with Stat3 activation potential of the receptor. This finding led to identification of Xenopus Stat3 (Xstat3), which showed a 95% homology to its murine and human counterparts, at the amino acid level, and was expressed from the one-cell stage throughout development. The mechanism of gp130/XStat3-mediated ventralization proved to be independent of BMP-4. gp130/Xstat3 stimulation inhibited Smad2-induced ectopic axis formation in embryos and Smad2-dependent luciferase activity. A dominant-negative Stat3, in contrast, dorsalized Xenopus embryos, resulting in ectopic axis formation. We propose that Stat3-mediated signaling has the capacity to modify dorsoventral patterning in the early development of Xenopus. 相似文献
69.
Bauer Paul J.; Schauf Heike; Schwarzer Andreas; Brown Joel E. 《American journal of physiology. Cell physiology》1999,276(3):C558
Na+/Ca2+exchange has been investigated in squid(Loligopealei) rhabdomeric membranes.Ca2+-containing vesicles have beenprepared from purified rhabdomeric membranes by extrusion throughpolycarbonate filters of 1-µm pore size. After removal of externalCa2+, up to 90% of the entrappedCa2+ could be specificallyreleased by the addition of Na+;this finding indicates that most of the vesicles containedNa+/Ca2+exchanger. The Na+-inducedCa2+ efflux had a half-maximumvalue (K1/2) of~44 mM and a Hill coefficient of ~1.7. The maximalNa+-inducedCa2+ efflux was ~0.6 nmolCa2+ · s1 · mgprotein1. SimilarNa+-inducedCa2+ effluxes were measured ifK+ was replaced withLi+ orCs+. Vesicles loaded withCa2+ byNa+/Ca2+exchange also released this Ca2+byNa+/Ca2+exchange, suggesting thatNa+/Ca2+exchange operated in both forward and reverse modes. Limited proteolysis by trypsin resulted in a rate ofCa2+ efflux enhanced byapproximately fivefold when efflux was activated with 95 mM NaCl. For vesicles subjected to limited proteolysis by trypsin,Na+/Ca2+exchange was characterized by aK1/2 of ~25 mMand a Hill coefficient of 1.6. For these vesicles, the maximalNa+-inducedCa2+ efflux was about twice asgreat as in control vesicles. We conclude thatNa+/Ca2+exchange proteins localized in rhabdomeric membranes mediate Ca2+ extrusion in squid photoreceptors. 相似文献
70.