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1.
Background
Protein translocation across the membrane of the Endoplasmic Reticulum (ER) is the first step in the biogenesis of secretory and membrane proteins. Proteins enter the ER by the Sec61 translocon, a proteinaceous channel composed of three subunits, α, β and γ. While it is known that Sec61α forms the actual channel, the function of the other two subunits remains to be characterized.Results
In the present study we have investigated the function of Sec61β in Drosophila melanogaster. We describe its role in the plasma membrane traffic of Gurken, the ligand for the Epidermal Growth Factor (EGF) receptor in the oocyte. Germline clones of the mutant allele of Sec61β show normal translocation of Gurken into the ER and transport to the Golgi complex, but further traffic to the plasma membrane is impeded. The defect in plasma membrane traffic due to absence of Sec61β is specific for Gurken and is not due to a general trafficking defect.Conclusion
Based on our study we conclude that Sec61β, which is part of the ER protein translocation channel affects a post-ER step during Gurken trafficking to the plasma membrane. We propose an additional role of Sec61β beyond protein translocation into the ER. 相似文献2.
Sequence of a cDNA for mouse thymidylate synthase reveals striking similarity with the prokaryotic enzyme 总被引:11,自引:0,他引:11
Perryman SM; Rossana C; Deng TL; Vanin EF; Johnson LF 《Molecular biology and evolution》1986,3(4):313-321
We report the nucleotide sequence of a cloned cDNA, pMTS-3, that contains a
1-kb insert corresponding to mouse thymidylate synthase (E.C. 2.1.1.45).
The open reading frame of 921 nucleotides from the first AUG to the
termination codon specifies a protein with a molecular mass of 34,962
daltons. The predicted amino acid sequence is 90% identical with that of
the human enzyme. The mouse sequence also has an extremely high degree of
similarity (as much as 55% identity) with prokaryotic thymidylate synthase
sequences, indicating that thymidylate synthase is among the most highly
conserved proteins studied to date. The similarity is especially pronounced
(as much as 80% identity) in the 44-amino-acid region encompassing the
binding site for deoxyuridylic acid. The cDNA sequence also suggests that
mouse thymidylate synthase mRNA lacks a 3' untranslated region, since the
termination codon, UAA, is followed immediately by a poly(A) segment.
相似文献
3.
Yiin JH Schubauer-Berigan MK Silver SR Daniels RD Kinnes GM Zaebst DD Couch JR Kubale TL Chen PH 《Radiation research》2005,163(6):603-613
Significantly elevated lung cancer deaths and statistically significantly positive linear trends between leukemia mortality and radiation exposure were reported in a previous analysis of Portsmouth Naval Shipyard workers. The purpose of this study was to conduct a modeling-based analysis that incorporates previously unanalyzed confounders in exploring the exposure-response relationship between cumulative external ionizing radiation exposure and mortality from these cancers among radiation-monitored workers in this cohort. The main analyses were carried out with Poisson regression fitted with maximum likelihood in linear excess relative risk models. Sensitivity analyses varying model components and using other regression models were conducted. The positive association between lung cancer risk and ionizing radiation observed previously was no longer present after adjusting for socioeconomic status (smoking surrogate) and welding fume and asbestos exposures. Excesses of leukemia were found to be positively, though not significantly, associated with external ionizing radiation, with or without including potential confounders. The estimated excess relative risk was 10.88% (95% CI -0.90%, 38.77%) per 10 mSv of radiation exposure, which was within the ranges of risk estimates in previous epidemiological studies (-4.1 to 19.0%). These results are limited by many factors and are subject to uncertainties of the exposure and confounder estimates. 相似文献
4.
Kubale TL Daniels RD Yiin JH Couch J Schubauer-Berigan MK Kinnes GM Silver SR Nowlin SJ Chen PH 《Radiation research》2005,164(6):810-819
A nested case-control study using conditional logistic regression was conducted to evaluate the exposure-response relationship between external ionizing radiation exposure and leukemia mortality among civilian workers at the Portsmouth Naval Shipyard (PNS), Kittery, Maine. The PNS civilian workers received occupational radiation exposure while performing construction, overhaul, repair and refueling activities on nuclear-powered submarines. The study age-matched 115 leukemia deaths with 460 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992. In addition to radiation doses received in the workplace, a secondary analysis incorporating doses from work-related medical X rays and other occupational radiation exposures was conducted. A significant positive association was found between leukemia mortality and external radiation exposure, adjusting for gender, radiation worker status, and solvent exposure duration (OR = 1.08 at 10 mSv of exposure; 95% CI = 1.01, 1.16). Solvent exposure (including benzene and carbon tetrachloride) was also significantly associated with leukemia mortality adjusting for radiation dose, radiation worker status, and gender. Incorporating doses from work-related medical X rays did not change the estimated leukemia risk per unit of dose. 相似文献
5.
Marie Terpager D. Jason Scholl Valentina Kubale Lene Martini Christian E. Elling 《Journal of receptor and signal transduction research》2013,33(5):235-245
7TM receptors are easily fused to proteins such as G proteins and arrestin but because of the fact that their terminals are found on each side of the membrane they cannot be joined directly in covalent dimers. Here, we use an artificial connector comprising a transmembrane helix composed of Leu-Ala repeats flanked by flexible spacers and positively charged residues to ensure correct inside-out orientation plus an extracellular HA-tag to construct covalently coupled dimers of 7TM receptors. Such 15 TM concatameric homo- and heterodimers of the β2-adrenergic and the NK1 receptors, which normally do not dimerize with each other, were expressed surprisingly well at the cell surface, where they bound ligands and activated signal transduction in a manner rather similar to the corresponding wild-type receptors. The concatameric heterodimers internalized upon stimulation with agonists for either of the protomers, which was not observed upon simple coexpression of the two receptors. It is concluded that covalently joined 7TM receptor dimers with surprisingly normal receptor properties can be constructed with use of an artificial transmembrane connector, which perhaps can be used to fuse other membrane proteins. 相似文献
6.
Results have been inconsistent between studies of lung cancer risk and ionizing radiation exposures among workers at the Portsmouth Naval Shipyard (PNS). The purpose of this nested case-control study was to evaluate the relationship between lung cancer risk and external ionizing radiation exposure while adjusting for potential confounders that included gender, radiation monitoring status, smoking habit surrogates (socioeconomic status and birth cohort), welding fumes and asbestos. By incidence density sampling, we age-matched 3,291 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992 with 1,097 lung cancer deaths from among the same cohort. Analyses using conditional logistic regression were conducted in various model forms: log-linear (main), linear excess relative risk (ERR), and categorical. Lung cancer risk was positively associated with occupational dose (OR = 1.02 at 10 mSv; 95% CI 0.99- 1.04) but flattened after the inclusion of work-related medical X-ray doses (OR = 1.00; 95% CI 0.98-1.03) in multivariate analyses. Similar risk estimates were observed in the linear ERR model at 10 mSv of cumulative exposure with a 15-year lag. 相似文献
7.
8.
Role of the reticulum in the stability and shape of the isolated human erythrocyte membrane 总被引:12,自引:7,他引:5
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In order to examine the widely held hypothesis that the reticulum of proteins which covers the cytoplamsic surface of the human erythrocyte membrane controls cell stability and shape, we have assessed some of its properties. The reticulum, freed of the bilayer by extraction with Triton X-100, was found to be mechanically stable at physiological ionic strength but physically unstable at low ionic strength. The reticulum broke down after a characteristic lag period which decreased 500-fold between 0 degrees and 37 degrees C. The release of polypeptide band 4.1 from the reticulum preceded that of spectrin and actin, suggesting that band 4.1 might stabilize the ensemble but is not essential to its integrity. The time-course of breakdown was similar for ghosts, the reticulum inside of ghosts, and the isolated reticulum. However, at very low ionic strength, the reticulum was less stable within the ghost than when free; at higher ionic strength, the reverse was true. Over a wide range of conditions the membrane broke down to vesicles just as the reticulum disintegrated, presumably because the bilayer was mechanically stabilized by this network. The volume of both ghosts and naked reticula varied inversely and reversibly with ionic strength. The volume of the naked reticulum varied far more widely than the ghost, suggesting that its deformation was normally limited by the less extensible bilayer. The contour of the isolated reticulum was discoid and often dimpled or indented, as visualized in the fluorescence microscope after labeling of the ghosts with fluoroscein isothiocyanate. Reticula derived from ghosts which had lost the ability to crenate in isotonic saline were shriveled, even though the bilayer was smooth and expanded. Conversly, ghosts crenated by dinitrophenol yielded smooth, expanded reticula. We conclude that the reticulum is a durable, flexible, and elastic network which assumes and stabilizes the contour of the membrane but is not responsible for its crenation. 相似文献
9.
Molecular evolution of a multigene family in group A streptococci 总被引:15,自引:0,他引:15
The emm genes are members of a gene family in group A streptococci (GAS)
that encode for antiphagocytic cell-surface proteins and/or
immunoglobulin-binding proteins. Previously sequenced genes in this family
have been named "emm," "fcrA," "enn," "arp," "protH," and "mrp"; herein
they will be referred to as the "emm gene family." The genes in the emm
family are located in a cluster occupying 3-6 kb between the genes mry and
scpA on the chromosome of Streptococcus pyogenes. Most GAS strains contain
one to three tandemly arranged copies of emm-family genes in the cluster,
but the alleles within the cluster vary among different strains.
Phylogenetic analysis of the conserved sequences at the 3' end of these
genes differentiates all known members of this family into four
evolutionarily distinct emm subfamilies. As a starting point to analyze how
the different subfamilies are related evolutionarily, the structure of the
emm chromosomal region was mapped in a number of diverse GAS strains by
using subfamily-specific primers in the polymerase chain reaction. Nine
distinct chromosomal patterns of the genes in the emm gene cluster were
found. These nine chromosomal patterns support a model for the evolution of
the emm gene family in which gene duplication followed by sequence
divergence resulted in the generation of four major-gene subfamilies in
this locus.
相似文献
10.
Brigida TL Lucena Billy M dos Santos João LS Moreira Ana Paula B Moreira Alvaro C Nunes Vasco Azevedo Anderson Miyoshi Fabiano L Thompson Marcos Antonio de MoraisJunior 《BMC microbiology》2010,10(1):298