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The Notch signaling pathway plays a central role in animal growth and patterning, and its deregulation leads to many human diseases, including cancer. Mutations in the tumor suppressor lethal giant discs (lgd) induce strong Notch activation and hyperplastic overgrowth of Drosophila imaginal discs. However, the gene that encodes Lgd and its function in the Notch pathway have not yet been identified. Here, we report that Lgd is a novel, conserved C2-domain protein that regulates Notch receptor trafficking. Notch accumulates on early endosomes in lgd mutant cells and signals in a ligand-independent manner. This phenotype is similar to that seen when cells lose endosomal-pathway components such as Erupted and Vps25. Interestingly, Notch activation in lgd mutant cells requires the early endosomal component Hrs, indicating that Hrs is epistatic to Lgd. These data suggest that Lgd affects Notch trafficking between the actions of Hrs and the late endosomal component Vps25. Taken together, our data identify Lgd as a novel tumor-suppressor protein that regulates Notch signaling by targeting Notch for degradation or recycling. 相似文献
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The deep-sea tube worm Riftia pachyptila Jones possesses a multi-hemoglobin system with three different extracellular Hbs: two dissolved in the vascular blood, V1 (ca. 3,500 kDa) and V2 (ca. 400 kDa), and one in the coelomic fluid, C1 (ca. 400 kDa). V1 Hb consists of four heme-containing, globin chains (b–e) and four linker chains (L1–L4). V2 and C1 Hbs are exclusively built from globin chains, six for V2 (a–f) and five for C1 (a–e). The complete amino acid sequence of the isolated monomeric globin chain b, common to all Riftia Hbs, has been determined by automated Edman degradation sequencing of the peptides derived by digestion with trypsin, chymotrypsin, thermolysin, and CNBr. This polypeptide chain is composed of 144 amino acid residues, providing a Mr of 16, 135.0 Da. Moreover, the primary sequence of chain b revealed 3 Cys residues at position 4, 75, and 134. Cys-4 and Cys-134 are located at positions where an intra-chain disulfide bridge is formed in all annelid, vestimentiferan, or pogonophoran chains, but Cys-75 is located at a unique position only found in three globin chains belonging to Lamellibrachia and Oligobrachia, a vestimentiferan and a pogonophoran. In both groups, Hbs can bind sulfide reversibly to fuel the chemosynthetic process of the symbiotic bacteria they harbor. Sulfide-binding experiments performed on purified Hb fractions (i.e., V1, V2, and C1 Hbs) suggest that free Cys residues on globin chains, and the numerous Cys found in linker chains, as determined previously by ESI-MS, may be the sulfide binding-sites. Blocking the free Cys by N-ethylmaleimide, we confirmed that free cysteines were involved in sulfide-binding but did not account for the whole sulfide-binding capacity of V1 Hb. Furthermore, a phylogenetic tree was constructed from 18 globin-like chains of annelid, vetimentiferan, and pogonophoran extracellular Hbs to clarify the systematic position of tubeworms. Riftia chain b clearly belongs to the “strain A” family with 30 to 80% identity with the other sequences analyzed. Its position in the tree confirmed a close relationship between vestimentiferan, pogonophoran, and annelid Hbs. Proteins 29:562–574, 1997. © 1997 Wiley-Liss, Inc. 相似文献
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Margaret McFall-Ngai Frederick Crescitelli James Childress Joseph Horwitz 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1986,159(6):791-800
Summary The present study is a morphological, biochemical and spectrophotometric characterization of the eye lens pigmentation in 45 specimens (11–88 mm in standard length) of the deep-sea hatchetfish,Argyropelecus affinis (Stomiiformes: Sternoptychidae). For comparison, we also examined available lenses of other members of the family Sternoptychidae, including three other species of the genusArgyropelecus, and two species of the genusSternoptyx. Lens pigmentation was observed in all specimens ofArgyropelecus spp. larger than about 36 mm in standard length, but was absent in allArgyropelecus spp. individuals less than 36 mm. However, lens pigmentation was not observed inSternoptyx specimens of any size. Detailed studies ofA. affinis indicated that (1) at 36 mm the nascent lens fiber cells, which are continually laid down over preexisting, unpigmented cells, begin incorporating pigment, and (2) the pigment concentration increases steadily as pigmented cells are added during lens growth. Spectrophotometric and biochemical data suggested that the pigment is a carotenoprotein complex, the carotenoid-like chromophore being strongly associated with a specific soluble lens protein, alpha crystallin. While the lens coloration in these fishes is age-related, analyses of the retinal visual pigment revealed no concomitant age-related change in the peak wavelength of retinal sensitivity in these fishes. Our data on the spectral absorbance of the lens and visual pigment of these fishes suggest that the lens pigmentation acts as a short-wave filter to improve acuity of the visual system. 相似文献
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Brad A. Seibel Shana K. Goffredi James J. Childress 《Journal of experimental marine biology and ecology》2004,313(2):375-387
The majority of squid families (Teuthoidea: Cephalopoda) exchange sodium for ammonium, creating a low-density fluid that imparts lift for neutral buoyancy. However, previous methods for measuring ammonium did not distinguish between NH4+ and various other amine compounds. The present study, using single column ion chromatography, reassessed the cation concentrations in several midwater cephalopod species. High NH4+ levels were confirmed for histioteuthid, cranchiid, and chiroteuthid and related squids. A strong relationship is reported between ammonium content and body mass in Histioteuthis heteropsis, suggesting a gradual accumulation of ammonium coincident with an ontogenetic migration to greater depths. The bathypelagic squids Bathyteuthis abyssicola and Bathyteuthis berryi, on the other hand, contained very little ammonium but rather contained large quantities of an as yet unidentified cation. The ecological significance of this compound is not yet known. Morphology in Bathyteuthid squids suggests that the unknown cation is contained intracellularly and so, unlike sequestered ammonia, does not diminish the space available for muscle tissue. Accordingly, protein measurements in B. berryi mantle muscle are on par with shallower-living muscular squids, and in situ submersible observations reveal strong locomotory abilities relative to other deep-water squids. 相似文献
89.
D. Childress 《Molecular & general genetics : MGG》1973,121(2):133-138
Summary Females homozygous and heterozygous for the B
S translocation were tested to determine the extent of the intra- and interchromosomal effects caused by the rearrangement. The heterozygous translocation produces an increase in crossing over at the tip of the X and in the centromere region of chromosome 2. The homozygous translocation has no effect on crossing over in these regions, but an unexpected increase is observed near the centromere region of the B
S segment. This result is not predicted by the time-delay model for interchromsomal effects.Supported by USPHS Training Grant 5T1 GM 1145-05 and NSF GB 18786. 相似文献
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