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Scott P. Lawrence Nicholas A. Bright J. Paul Luzio Katherine Bowers 《Molecular biology of the cell》2010,21(20):3540-3551
The pH and lumenal environment of intracellular organelles is considered essential for protein sorting and trafficking through the cell. We provide the first evidence that a mammalian NHE sodium (potassium)/proton exchanger, NHE8, plays a key role in the control of protein trafficking and endosome morphology. At steady state, the majority of epitope-tagged NHE8 was found in the trans-Golgi network of HeLa M-cells, but a proportion was also localized to multivesicular bodies (MVBs). Depletion of NHE8 in HeLa M-cells with siRNA resulted in the perturbation of MVB protein sorting, as shown by an increase in epidermal growth factor degradation. Additionally, NHE8-depleted cells displayed striking perinuclear clustering of endosomes and lysosomes, and there was a ninefold increase in the cellular volume taken up by LAMP1/LBPA-positive, dense MVBs. Our data points to a role for the ion exchange activity of NHE8 being required to maintain endosome morphology, as overexpression of a nonfunctional point mutant protein (NHE8 E225Q) resulted in phenotypes similar to those seen after siRNA depletion of endogenous NHE8. Interestingly, we found that depletion of NHE8, despite its function as a sodium (potassium)/proton antiporter, did not affect the overall pH inside dense MVBs. 相似文献
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John G. Neuhoff Katherine L. Long Rebecca C. Worthington 《Evolution and human behavior》2012,33(4):318-322
Listeners consistently perceive approaching sounds to be closer than they actually are and perceptually underestimate the time to arrival of looming sound sources. In a natural environment, this underestimation results in more time than expected to evade or engage the source and affords a “margin of safety” that may provide a selective advantage. However, a key component in the proposed evolutionary origins of the perceptual bias is the appropriate timing of anticipatory motor behaviors. Here we show that listeners with poorer physical fitness respond sooner to looming sounds and with a larger margin of safety than listeners with better physical fitness. The anticipatory perceptual bias for looming sounds is negatively correlated with physical strength and positively correlated with recovery heart rate (a measure of aerobic fitness). The results suggest that the auditory perception of looming sounds may be modulated by the response capacity of the motor system. 相似文献
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A conceptual framework for comparing species assemblages in native and exotic habitats 总被引:4,自引:0,他引:4
Exotic (nonnative) species are known to have a wide variety of impacts on native biota. One potential set of impacts that have been poorly studied are the effects of replacing native habitat-providing species with exotic ones, e.g. when native trees that compose a woodland are replaced by an exotic tree plantation. Here we develop a graphical model that can be used to explore how multiple taxonomic components (such as birds, mammals and plants) respond to such changes. We suggest that four categorical responses are possible, with respect to changes in species richness (or other quantitative measures) of taxonomic groups within species assemblages. First, that each taxonomic group compared between habitats will be relatively unchanged, e.g. have equivalent values of species richness. Second, that a decrease (for example in species richness) of one group will be compensated for by an increase (in species richness) of another group. Third, that one or more groups will decrease without any compensated increases in other groups. Fourth, that one or more groups will increase without any compensated decreases in other groups. We provide empirical support for 3 of these 4 responses, with respect to measures of species richness, with much evidence for equivalency between habitats. These types of comparisons should provide a valuable tool for evaluating 1) the efficacy of environmental mitigation efforts that artificially create or restore habitats and 2) the types of changes that have occurred over time or across space as native habitat-producing species are replaced by exotic ones. Finally, this conceptual framework should help to broaden the range of possible changes considered by ecologists who study the impacts of exotic species. 相似文献
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Insulin stimulated autophosphorylation of the beta-subunit of the insulin receptor purified from Fao hepatoma cells or purified from Chinese hamster ovary (CHO/HIRC) or Swiss 3T3 (3T3/HIRC) cells transfected with the wild-type human insulin receptor cDNA. Autophosphorylation of the purified receptor occurred in at least two regions of the beta-subunit: the regulatory region containing Tyr-1146, Tyr-1150, and Tyr-1151, and the C-terminus containing Tyr-1316 and Tyr-1322. In the presence of antiphosphotyrosine antibody (alpha-PY), autophosphorylation of the purified receptor was inhibited nearly 80% during insulin stimulation. Tryptic peptide mapping showed that alpha-PY inhibited autophosphorylation of both tyrosyl residues in the C-terminus and one tyrosyl residue in the regulatory region, either Tyr-1150 or Tyr-1151. Thus, a bis-phosphorylated form of the regulatory region accumulated in the presence of alpha-PY, which contained Tyr(P)-1146 and either Tyr(P)-1150 or 1151. In intact Fao, CHO/HIRC, and 3T3/HIRC cells, insulin stimulated tyrosyl phosphorylation of the beta-subunit of the insulin receptor. Tryptic peptide mapping indicated that the regulatory region of the beta-subunit was mainly (greater than 80%) bis-phosphorylated; however, all three tyrosyl residues of the regulatory region were phosphorylated in about 20% of the receptors. As the phosphotransferase was activated by tris-phosphorylation but not bis-phosphorylation of the regulatory region of the beta-subunit (White et al.: Journal of Biological Chemistry 263:2969-2980, 1988), the extent of autophosphorylation in the regulatory region may play an important regulatory role during signal transmission in the intact cell. 相似文献
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