Folimycin (Concanamycin A), an Inhibitor of V-Type H+-ATPase, Blocks Cell-Surface Expression of Virus-Envelope Glycoproteins

Muroi, Makoto; Takasu, Atsunori; Yamasaki, M.; Takatsuki, Akira

doi:10.1006/bbrc.1993.1724

Cited by 43 publications

(34 citation statements)

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“…The nonstructural virus protein (NS) was not detected in the medium fractions, indicating that release of G protein into the control mediumfraction is not a consequence of cytopathic effect of VSV multiplication. The G protein accumulated in folimycin-treated cells was resistant to proteinase K added extracellularly (16). This result indicates that folimycin blocks cell-surface expression of G protein.…”

Section: Resultsmentioning

confidence: 85%

“…The possibility that folimycin blocks release of G protein from the cell surface without affecting its cell-surface expression was excluded by the following observations. Extracellularly added proteinase K digested the G protein expressed on the cell surface of control cells, but the cell-associated G protein synthesized in the presence of folimycin was resistant to this treatment (16). Whenthe fate of the intracellular G protein was followed by indirect immunofluorescencetechnique, no significant decrease of the intracellularly accumulated Gprotein was observed on chase in the presence of folimycin and cycloheximide while a great diminution was detected with the control cells (Fig.…”

Section: Discussionmentioning

confidence: 92%

“…But very restricted specific inhibitors are nowavailable. Wehave searched for inhibitors that block cell-surface expression of glycoprotein and found folimycin in this search (16). Synthesis and intracellular translocation of viral glycoproteins have been studied as a model of membrane glycoprotein trafficking (2).…”

Section: Discussionmentioning

confidence: 99%

“…Folimycin (concanamycin A) was found in this screening study (16). Folimycin was initially isolated as an antifungal antibiotic (32).…”

mentioning

confidence: 90%

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Folimycin(Concanamycin A), a Specific Inhibitor of V-ATPase, Blocks Intracellular Translocation of the Glycoprotein of Vesicular Stomatitis Virus before Arrival to the Golgi Apparatus.

Muroi

Shiragami

Nagao

et al. 1993

Cell Struct. Funct.

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Key words: folimycin/concanamycinA/intracellular translocation of glycoproteins/vacuolar-type ATPase/vesicular stomatitis virus/the Golgi apparatus ABSTRACT. Folimycin (concanamycin A) specifically inhibited vacuolar-type ATPase as far as examined. Folimycin blocked excretion of the glycoprotein (G protein) of vesicular stomatitis virus into the medium and, instead, G protein was accumulated intracellularly.The intracellularly accumulated G protein electrophoresed a little faster than mature one. The N-glycan of the G protein was endoglycosidase H-sensitive, and terminal galactose and N-acetylglucosamine were not detected essentially on sequential digestion with exoglycosidases, indicating that processings known to occur in the Golgi apparatus do not take place in the presence of folimycin. The oligosaccharide chain of the G protein was determined to have a composition of Man8GlcNAc2 as analyzed by Bio-Gel P-4 column chromatography and high-performance liquid chromatography following digestion with a-and then with /5-mannosidase. Activities of mannosidase I and glycosyltransferases prepared from baby hamster kidney cells were not inhibited as far as examined, indicating that the incompleteness of the N-glycosidic chain in folimycin-treated cells is not caused by inhibition of processing enzymes. Taken together these observations suggest that folimycin blocks the intracellular translocation of G protein before the step of trimming by mannosidase I which is confined to the cis compartment of the Golgi. The intracellular localization of G protein as revealed by fluorescence microscopy was in good accordance with this assumption.

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Section: Resultsmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

“…Folimycin (concanamycin A) was found in this screening study (16). Folimycin was initially isolated as an antifungal antibiotic (32).…”

mentioning

confidence: 90%

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Folimycin(Concanamycin A), a Specific Inhibitor of V-ATPase, Blocks Intracellular Translocation of the Glycoprotein of Vesicular Stomatitis Virus before Arrival to the Golgi Apparatus.

Muroi

Shiragami

Nagao

et al. 1993

Cell Struct. Funct.

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“…To ascertain whether a similar mechanism is involved in the heterologous transfectants, COS-2A cells were allowed to internalize labeled zymosan and then treated with concanamycin, a potent and selective inhibitor of V-ATPases (33). As before, the phagosomal location of the particle was first verified (Fig.…”

Section: Resultsmentioning

confidence: 99%

Phagosomal Maturation, Acidification, and Inhibition of Bacterial Growth in Nonphagocytic Cells Transfected with FcγRIIA Receptors

Downey¹,

Botelho²,

Butler³

et al. 1999

Journal of Biological Chemistry

111

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Opsonization was essential for bacterial internalization, implying that it occurred by Fc␥RIIA-mediated phagocytosis, as opposed to invasion. Uptake into phagolysosomes was associated with inhibition of bacterial growth, due at least in part to the low intraphagosomal pH. These studies indicate that the biochemical events that follow receptor-mediated particle internalization in cells transfected with Fc␥RIIA receptors closely resemble the process of phagosomal maturation in neutrophils and macrophages. Fc␥RIIA-transfected cells can, therefore, be used as a model for the study of additional aspects of phagocyte biology.

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Chemistry and Biod iversity of the Biologically Active Natural Glycosides

Dembitsky¹

2004

Chemistry & Biodiversity

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Folimycin (Concanamycin A), an Inhibitor of V-Type H+-ATPase, Blocks Cell-Surface Expression of Virus-Envelope Glycoproteins

Cited by 43 publications

References 0 publications

Folimycin(Concanamycin A), a Specific Inhibitor of V-ATPase, Blocks Intracellular Translocation of the Glycoprotein of Vesicular Stomatitis Virus before Arrival to the Golgi Apparatus.

Folimycin(Concanamycin A), a Specific Inhibitor of V-ATPase, Blocks Intracellular Translocation of the Glycoprotein of Vesicular Stomatitis Virus before Arrival to the Golgi Apparatus.

Phagosomal Maturation, Acidification, and Inhibition of Bacterial Growth in Nonphagocytic Cells Transfected with FcγRIIA Receptors

Chemistry and Biod iversity of the Biologically Active Natural Glycosides

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