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101.
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Modulation of postendocytic sorting of G protein-coupled receptors   总被引:1,自引:0,他引:1  
Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding protein (G protein)-coupled receptor-associated sorting protein (GASP). Disruption of the DOR-GASP interaction through receptor mutation or overexpression of a dominant negative fragment of GASP inhibited receptor trafficking to lysosomes and promoted recycling. The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein-coupled receptors.  相似文献   
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Aggregated alpha-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders. Using antibodies to specific nitrated tyrosine residues in alpha-synuclein, we demonstrate extensive and widespread accumulations of nitrated alpha-synuclein in the signature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated alpha-synuclein is present in the major filamentous building blocks of these inclusions, as well as in the insoluble fractions of affected brain regions of synucleinopathies. The selective and specific nitration of alpha-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.  相似文献   
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Cells crawl by coupling protrusion of their leading edge with retraction of their cell body. Protrusion is generated by the polymerization and bundling of filaments, but the mechanism of retraction is less clear. We have reconstituted retraction in vitro by adding Yersinia tyrosine phosphatase to the major sperm protein-based motility apparatus assembled from Ascaris sperm extracts. Retraction in vitro parallels that observed in vivo and is generated primarily by disassembly and rearrangement of the cytoskeleton. Therefore, cytoskeletal dynamics alone, unassisted by conventional motors, are able to generate both of these central components of amoeboid locomotion.  相似文献   
108.
At orbit insertion on 14 November 1971 the Martian surface was largely obscured by a dust haze with an extinction optical depth that ranged from near unity in the south polar region to probably greater than 2 over most of the planet. The only features clearly visible were the south polar cap, one dark, spot in Nix Olympica, and three dark spots in the Tharsis region. During the third week the atmosphere began to clear and surface visibility improved, but contrasts remained a fraction of their normal value. Each of the dark spots that apparently protrude through most of the dust-filled atmosphere has a crater or crater complex in its center. The craters are rimless and have featureless floors that, in the crater complexes, are at different levels. The largest crater within the southernmost spot is approximately 100 kilometers wide. The craters apparently were formed by subsidence and resemble terrestrial calderas. The south polar cap has a regular margin, suggsting very flat topography. Two craters outside the cap have frost on their floors; an apparent crater rim within the cap is frost free, indicating preferentia loss of frost from elevated ground. If this is so then the curvilinear streaks, which were frost covered in 1969 and are now clear of frost, may be low-relief ridges. Closeup pictures of Phobos and Deimos show that Phobos is about 25 +/-5 by 21 +/-1 kilometers and Deimos is about 13.5 +/- 2 by 12.0 +/-0.5 kilometers. Both have irregular shapes and are highly cratered, with some craters showing raised rims. The satellites are dark objects with geometric albedos of 0.05.  相似文献   
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The residual frost caps of Mars are probably water-ice. They may be the source of the water vapor associated with seasonal polar hoods. A permanent reservoir of solid CO(2) is also probably present within the north residual cap and may comprise a mass of CO(2) some two to five times that of the present atmosphere of Mars. The martian atmospheric pressure is probably regulated by the temperature of the reservoir and not by the annual heat balance of exposed solid CO(2) (37). The present reservoir temperature presumably reflects a long-term average of the polar heat balance. The question of a large permanent north polar cap is reexamined in light of the Mariner 9 data. The lower general elevation of the north polar region compared to the south and the resulting occurrence in the north of a permanent CO(2) deposit are probably responsible for the differences in size and shape of the two residual caps. The details of the processes involved are less apparent, however. It might be argued that the stability of water-ice deposits depends on both insolation and altitude. The present north and south residual caps should be symmetrically located with respect to such a hypothetical stability field. However, the offset of the south cap from the geometrical pole, the non-symmetrical outline of the north cap, and the apparently uniform thickness of the thin, widespread water-ice all argue against control by simple solid-vapor equilibrium of water under present environmental conditions. We think that the present location of the water-ice may reflect, in part, the past location of the permanent CO(2) reservoir. The extreme stability of polar water-ice deposits increases the likelihood that past environmental conditions may be recorded there. Detailed information on elevations in the vicinity of the residual caps is needed before we can further elucidate the nature and history of the residual caps. This, along with measurements of polar infrared emission, should be given high priority in future missions to Mars. Two conclusions follow from the limitation of the mass of solid CO(2) on Mars at present to two to five times the mass of CO(2) in the atmosphere. If all of this CO(2) was entirely sublimated into the atmosphere as a result of hypothetical astronomical or geophysical effects, the average surface pressure would increase to 15 to 30 mbar. Although such a change would have considerable significance for eolian erosion and transportation, there seems to be little possibility that a sufficiently earthlike atmosphere could result for liquid water to become an active erosional agent, as postulated by Milton (38). The pressure broadening required for a green-house effect requires at least 10 to 20 times more pressure (39). If liquid water was ever active in modifying the martian surface, it must have been at an earlier epoch, before the present, very stable CO(2)/H(2)O system developed. There can be no intermittent earthlike episodes now. Furthermore, the present abundance of CO(2) on Mars may be an indicator of the cumulative evolution of volatiles to the surface of the planet (40). Thus, even the possibility of an earlier earth-like episode is dimmed. On Mars, the total CO(2) definitely outgassed has evidently been about 60 +/- 20 g/cm(2). On the earth, about 70 +/- 30 kg/cm(2) of CO(2) have been released to the surface (41). Hence, the total CO(2) devolved by Mars per unit area is about 0.1 percent of that evolved by the earth. Thus, the observational limits we place on solid CO(2) presently located under the north residual cap also may constitute considerable constraints on the total differentiation and devolatilization of the planet. If they are valid, it would seem unlikely that Mars has devolatilized at all like the earth, or ever experienced an earthlike environment on its surface.  相似文献   
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