Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0038362 (stomatitis)
8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycoprotein (G) of vesicular stomatitis virus (VSV) is synthesized on membrane-bound polyribosomes. Approximately 30 min after its synthesis, it reaches the surface plasma membrane where it is incorporated into budding virus. The first part of this paper focuses on the 2 intracellular, membrane-bound, glycosylated forms of the glycoprotein which are intermediates in its biogenesis. All glycosylation and processing is completed in the smooth microsome fraction before the protein reaches the surface. Next, we turn to the mechanism by which G is synthesized on membrane-bound polyribosomes. All of the G mRNA is bound to membranes, and studies with puromycin suggest that this attachment of G mRNA is mediated by the nascent glycoprotein chain. After its synthesis G is a transmembrane protein with about 30 amino acids at the carboxyl terminus remaining on the cytoplasmic side of the endoplasmic reticulum. Since 95% of the glycoprotein, containing the carbohydrate residues, is resistant to attack by external proteases, it appears to be within the lumen of the endoplasmic reticulum or embedded within the lipid bilayer. Finally, we show that synthesis, glycosylation, and proper asymmetric insertion of G into the ER can be achieved in cell-free extracts. Both glycosylation of G and proper insertion into the ER membrane in this cell-free system require concomitant protein synthesis.
...
PMID:Membrane assembly: synthesis and intracellular processing of the vesicular stomatitis viral glycoprotein. 21 48

Translation of mRNA encoding vesicular stomatitis virus envelope glycoprotein G by as membrane-free ribosomal extract obtained from HeLa cells yielded a nonglycosylated protein (G1 (Mr 63,000). In the presence of added microsomal membranes, G1 was converted to the glycosylated protein (G2 (Mr 67,000) which is inserted in the membrane vesicles as a transmembrane protein. Labeling with methionine donated by wheat germ initiator tRNA1Met showed that G1 but not G2 contains methionine in the NH2-terminal position. Determination of the NH2-terminal sequence of G1, G2, and G showed that a leader peptide of 16 amino acids is present in G1 but absent from the glycosylated proteins G2 and G. This leader peptide contains at least 62% hydrophobic amino acids and is removed presumably during insertion of G1 into the membrane.
...
PMID:Synthesis and assembly of membrane glycoproteins: presence of leader peptide in nonglycosylated precursor of membrane glycoprotein of vesicular stomatitis virus. 21 9

The components of biological membranes are asymmetrically distributed between the membrane surfaces. Proteins are absolutely asymmetrical in that every copy of a polypeptide chain has the same orientation in the membrane, and lipids are nonabsolutely asymmetrical in that almost every type of lipid is present on both sides of the bilayer, but in different and highly variable amounts. Asymmetry is maintained by lack of transmembrane diffusion. Two types of membrane proteins, called ectoproteins and endoproteins, are distinguished. Biosynthetic pathways for both types of proteins and for membrane lipids are inferred from their topography and distribution in the formed cells. Note added in proof. A cell-free system has now been developed which permits the mechanisms of membrane protein assembly to be studied (108). The membrane glycoprotein of vesicular stomatitis virus has been synthesized by wheat germ ribosomes in the presence of rough endoplasmic reticulum from pancreas. The resulting polypeptide is incorporated into the membrane, spans the lipid bilayer asymmetrically, and is glycosylated (108). The amino terminal portion of this transmembrane protein is found inside the endoplasmic reticulum vesicle, while the carboxyl terminal portion is exposed on the outer surface of the vesicle. Furthermore, addition of the glycoprotein to membranes after protein synthesis does not result in incorporation of the protein into the membrane in the manner described above (108). Consequently, protein synthesis and incorporation into the membrane must be closely coupled. Indeed, using techniques to synchronize the growth of nascent polypeptides, it has been shown (109) that no more than one-fourth of the glycoprotein chain can be made in the absence of membranes and still cross the lipid bilayer when chains are subsequently completed in the presence of membranes. These findings demonstrate directly that the extracytoplasmic portion of an ectoprotein can cross the membrane only during biosynthesis, and not after.
...
PMID:Membrane asymmetry. 40 30

The envelope glycoprotein (G protein) of vesicular stomatitis virus is a transmembrane protein that exists as a trimer of identical subunits in the virus envelope. We have examined the effect of modifying the environment surrounding the membrane-spanning sequence on the association of G protein subunits using resonance energy transfer. G protein subunits were labeled with either fluorescein isothiocyanate or rhodamine isothiocyanate. When the labeled G proteins were mixed in the presence of the detergent octyl glucoside, mixed trimers containing both fluorescent labels were formed as a result of subunit exchange, as shown by resonance energy transfer between the two labels. In contrast when fluorescein- and rhodamine-labeled G proteins were mixed in the presence of Triton X-100, no resonance energy transfer was observed, indicating that subunit exchange did not occur in Triton X-100 micelles. However, if labeled G proteins were first mixed in the presence of octyl glucoside, energy transfer persisted after dilution with buffer containing Triton X-100. This result indicates that the G protein subunits remained associated in Triton X-100 micelles and that the failure to undergo subunit exchange was due to lack of dissociation of G protein subunits. Chemical cross-linking experiments confirmed that G protein was trimeric in the presence of Triton X-100. The efficiency of resonance energy transfer between labeled G protein was higher when G proteins were incorporated into dimyristoylphosphatidylcholine liposomes compared to detergent micelles. This result indicates that the labels exist in a more favorable environment for energy transfer in membranes than in detergent micelles.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Subunit interactions of vesicular stomatitis virus envelope glycoprotein influenced by detergent micelles and lipid bilayers. 132 49

We have studied the role of a previously described tubulovesicular compartment near the cis-Golgi apparatus in endoplasmic reticulum (ER)-to-Golgi protein transport by light and immunoelectron microscopy in Vero cells. The compartment is defined by a 53-kDa transmembrane protein designated p53. When transport of the vesicular stomatitis virus strain ts045 G protein was arrested at 39.5 degrees C, the G protein accumulated in the ER but had access to the p53 compartment. At 15 degrees C, the G protein was exported from the ER into the p53 compartment which formed a compact structure composed of vesicular and tubular profiles in close proximity to the Golgi. Upon raising the temperature to 32 degrees C, the G protein migrated through the Golgi apparatus while the p53 compartment resumed its normal structure again. These results establish the p53 compartment as the 15 degrees C intermediate of the ER-to-Golgi protein transport pathway.
...
PMID:Identification of an intermediate compartment involved in protein transport from endoplasmic reticulum to Golgi apparatus. 196 13

Fluorescence recovery after photobleaching (FRAP) has been a powerful tool for characterizing the mobility of cell surface membrane proteins. However, the application of FRAP to the study of intracellular membrane proteins has been hampered by the lack of specific probes and their physical inaccessibility in the cytoplasm. We have measured the mobility of a model transmembrane protein, the temperature-sensitive vesicular stomatitis viral membrane glycoprotein (ts-O45-G), in transit from the endoplasmic reticulum (ER) to the Golgi complex. ts-O45-G accumulates in the ER at nonpermissive temperature (39.5 degrees C) and is transported via the Golgi complex to the surface upon shifting cells to the permissive temperature (31 degrees C). Rhodamine-labeled Fab fragments against a cytoplasmic epitope of ts-O45-G (rh-P5D4-Fabs) were microinjected into cells to visualize the intracellular viral membrane protein and to determine its mobility by FRAP with a confocal microscope. Moreover, we have measured the effects of microinjected antibodies against beta-COP on the mobility of ts-O45-G following release of the temperature block. FRAP was essentially complete when rh-P5D4-Fab-injected cells were bleached either following release of labeled ts-O45-G from the ER or upon its accumulation at 20 degrees C in the trans-Golgi network (TGN). In contrast, recovery was reduced by about one third when infected cells had been injected with antibodies that bind to beta-COP in vivo. The diffusion constant of mobile ts-O45-G under all conditions was approximately 10 x 10(-10) cm2/s. These results validate the feasibility of FRAP for the study of an intracellular transmembrane protein and provide the first evidence that such a protein is highly mobile.
...
PMID:The intracellular mobility of a viral membrane glycoprotein measured by confocal microscope fluorescence recovery after photobleaching. 792 37

p53/58 is a transmembrane protein that continuously recycles between the ER and pre-Golgi intermediates composed of vesicular-tubular clusters (VTCs) found in the cell periphery and at the cis face of the Golgi complex. We have generated an antibody that uniquely recognizes the p53/58 cytoplasmic tail. Here we present evidence that this antibody arrests the anterograde transport of vesicular stomatitis virus glycoprotein and leads to the accumulation of p58 in pre-Golgi intermediates. Consistent with a role for the KKXX retrieval motif found at the cytoplasmic carboxyl terminus of p53/58 in retrograde traffic, inhibition of transport through VTCs correlates with the ability of the antibody to block recruitment of COPI coats to the p53/58 cytoplasmic tail and to p53/58-containing membranes. We suggest that p53/58 function may be required for the coupled exchange of COPII for COPI coats during segregation of anterograde and retrograde transported proteins.
...
PMID:p53/58 binds COPI and is required for selective transport through the early secretory pathway. 915 66

Human T cell leukemia virus type I (HTLV-I) is a retrovirus that is not lysed by human serum or complement. It has not been determined, however, whether HTLV-I directly binds to complement components or whether it retains infectivity after incubation with human serum. We investigated the effects of human serum on the infectivity of cell-free HTLV-I produced by human and animal cells. Plating of vesicular stomatitis virus (HTLV-I) pseudotypes prepared in cat or human cells and formation of HTLV-I DNA after infection of cell-free HTLV-I produced by cat or human cells were markedly inhibited by treatment with fresh human serum, but not by heat-inactivated serum. HTLV-I infection was also inhibited by treatment with C2-, C3-, C6-, or C9-deficient serum, but not by C1q-deficient serum. Inhibitory activities of normal human serum against HTLV-I were neutralized by anti-C1q serum. Furthermore, purified C1q inhibited HTLV-I infection. The direct binding of C1q to HTLV-I was confirmed by comigration of C1q with HTLV-I virion upon sucrose density gradient ultracentrifugation of HTLV-I virion treated with C1q. Binding assay using synthetic envelope peptides indicated that C1q bound to an extramembrane region of the gp21 transmembrane protein. These findings indicate that the human complement component C1q inactivates HTLV-I infectivity.
...
PMID:Human complement component C1q inhibits the infectivity of cell-free HTLV-I. 982 May 53

Quantitative time-lapse imaging data of single cells expressing the transmembrane protein, vesicular stomatitis virus ts045 G protein fused to green fluorescent protein (VSVG-GFP), were used for kinetic modeling of protein traffic through the various compartments of the secretory pathway. A series of first order rate laws was sufficient to accurately describe VSVG-GFP transport, and provided compartment residence times and rate constants for transport into and out of the Golgi complex and delivery to the plasma membrane. For ER to Golgi transport the mean rate constant (i.e., the fraction of VSVG-GFP moved per unit of time) was 2.8% per min, for Golgi to plasma membrane transport it was 3.0% per min, and for transport from the plasma membrane to a degradative site it was 0.25% per min. Because these rate constants did not change as the concentration of VSVG-GFP in different compartments went from high (early in the experiment) to low (late in the experiment), secretory transport machinery was never saturated during the experiments. The processes of budding, translocation, and fusion of post-Golgi transport intermediates carrying VSVG- GFP to the plasma membrane were also analyzed using quantitative imaging techniques. Large pleiomorphic tubular structures, rather than small vesicles, were found to be the primary vehicles for Golgi to plasma membrane transport of VSVG-GFP. These structures budded as entire domains from the Golgi complex and underwent dynamic shape changes as they moved along microtubule tracks to the cell periphery. They carried up to 10,000 VSVG-GFP molecules and had a mean life time in COS cells of 3.8 min. In addition, they fused with the plasma membrane without intersecting other membrane transport pathways in the cell. These properties suggest that the post-Golgi intermediates represent a unique transport organelle for conveying large quantities of protein cargo from the Golgi complex directly to the plasma membrane.
...
PMID:Kinetic analysis of secretory protein traffic and characterization of golgi to plasma membrane transport intermediates in living cells. 985 46

The COPII coat complex found on endoplasmic reticulum (ER)-derived vesicles plays a critical role in cargo selection. We now address the potential role of biosynthetic cargo in modulating COPII coat assembly and vesicle budding. The ER accumulation of vesicular stomatitis glycoprotein (VSV-G), a transmembrane protein, or the soluble PiZ variant of alpha1-antitrypsin, reduced levels of general COPII vesicle formation in vivo. Consistent with this result, conditions that prevent the export of VSV-G from the ER led to a significant inhibition of general COPII vesicle budding from ER microsomes and the export of an endogenous recycling protein p58 in vitro. In contrast, synchronized export of VSV-G stimulated COPII vesicle budding both in vivo and in vitro. Under conditions where VSV-G is retained in the ER, we find that it can to be recovered in pre-budding complexes containing COPII components. These results suggest that the export of biosynthetic cargo is integrated with ER functions involved in protein folding and oligomerization. The ability of biosynthetic cargo to prevent or enhance ER export suggests that interactions of cargo with the COPII machinery contribute to the formation of vesicles budding from the ER.
...
PMID:Cargo can modulate COPII vesicle formation from the endoplasmic reticulum. 993 43


1 2 Next >>

---