Abstract
Brefeldin A (BFA) is a fungal metabolite that exerts generally inhibitory actions on membrane transport and induces the disappearance of the Golgi complex. Previously we have shown that BFA stimulates the ADP-ribosylation of two cytosolic proteins of 38 and 50 KD. The BFA-binding components mediating the BFA-sensitive ADP-ribosylation (BAR) and the effect of BFA on ARF binding to Golgi membranes have similar specificities and affinities for BFA and its analogues, suggesting that BAR may have a role in the cellular effects of BFA. To investigate this we used the approach to impair BAR activity by the use of BAR inhibitors. A series of BAR inhibitors was developed and their effects were studied in RBL cells treated with BFA. In addition to the common ADP-ribosylation inhibitors (nicotinamide and aminobenzamide), compounds belonging to the cumarin (novobiocin, cumermycin, dicumarol) class were active BAR inhibitors. All BAR inhibitors were able to prevent the BFA-induced redistribution of a Golgi marker (Helix pomatia lectin) into the endoplasmic reticulum, as assessed in immunofluorescence experiments. At the ultrastructural level, BAR inhibitors prevented the tubular-vesicular transformation of the Golgi complex caused by BFA. The potencies of these compounds in preventing the BFA effects on the Golgi complex were similar to those at which they inhibited BAR. Altogether these data support the hypothesis that BAR mediates at least some of the effects of BFA on the Golgi structure and function.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Klausner, R. D., J. G. Donaldson, & J. Lippincott-Schwartz. 1992. Brefeldin A: insights into the control of membrane traffic and organelle structure. J. Cell Biol. 116: 1071–1080.
Price, S. R., M. Nightingale, S.-C. Tsai, K. C. Williamson, R. Adamik, H.-C. Chen, J. Moss, & M. Vaughan. 1988. Proc. Natl. Acad. Sci. USA 85: 5488–5491.
Donaldson, J. G., J. Lippincott-Schwartz, G. S. Bloom, T. E. Kreis, & R. D. Klausner. 1990. Dissociation of a 110-kD peripheral membrane protein from the Golgi apparatus is an early event in brefeldin A action. J. Cell Biol. III: 2295–2306.
Donaldson, J. G., J. Lippincott-Schwartz, & R. D. Klausner. 1991. Guanine nucleotides modulate the effects of brefeldin A in semipermeable cells: regulation of the association of a 110-kD peripheral membrane protein with the Golgi apparatus. J. Cell Biol. 112: 579–588.
Donaldson, J. G., R. A. Kahn, J. Lippincott-Schwartz, & R. D. Klausner. 1991. Binding of ARF and p-COP to Golgi membranes: possible regulation by a trimeric G protein. Science 254: 1197–1199.
Donaldson, J. G., D. Finazzi, & R. D. Klausner. 1992. Brefeldin A inhibits Golgi membrane-catalysed exchange of guanine nucleotide onto ARF protein. Nature 360: 350–352.
Helms, J. B., & J. E. Rothman. 1992. Inhibition by brefeldin A of a Golgi membrane enzyme that catalyses exchange of guanine nucleotide bound to ARF. Nature 360: 352–354.
Kahn, R. A., & A. G. Gilman. 1984. Purification of a protein cofactor required for ADP-ribosylation of the stimulatory regulatory component of adenylate cyclase by cholera toxin. J. Biol. Chem. 259: 6228–6234.
Tsai, S.-C, M. Noda, R. Adamik, J. Moss, & M. Vaughan. 1987. Enhancement of choleragen ADP-ribosyl-transferase activities by guanyl nucleotides and a 19-kDa membrane protein. Proc. Natl. Acad. Sci. USA. 84:5139–5142.
Ueda, K., & O. Hayaishi. 1985. ADP-ribosylation. Annu. Rev. Biochem. 54: 73–100.
De Matteis, M. A., M. Di Girolamo, A. Colanzi, M. Pallas, G. Di Tullio, L. J. McDonald, J. Moss, G. Santini, S. Bannykh, D. Corda, & A. Luini. 1994. Stimulation of endogenous ADP-ribosylation by brefeldin A. Proc. Natl. Acad. Sci. USA 91: 1114–1118.
Colanzi, A., M. Di Girolamo, G. Santini, G. Sciulli, S. Santarone, M. Pallas, G. Di Tullio, S. Bannykh, D. Corda, M. A. De Matteis, & A. Luini. 1994. Brefeldin A, an inhibitor of vesicular traffic, stimulates the ADP-ribosylation of two cytosolic proteins. In GTPase-Controlled Molecular Machines, eds. D. Corda, H. Hamm, & A. Luini. Ares-Serono Symposia Publications, Rome, pp. 197–217.
Di Girolamo, M., M. G. Silletta, M. A. De Matteis, A. Braca, A. Colanzi, D. Pawlak, M. M. Rasenick, A. Luini, & D. Corda. 1995. Evidence that the 50-kDa substrate of brefeldin A-dependent ADP-ribosylation binds GTP and is modulated by the G-protein py subunit complex. Proc. Natl. Acad. Sci. USA.92: 7065–7069.
Mironov, A., A. Colanzi, S. Flati, I. Santone, A. Fusella, R. Polishchuk, A. Mironov Jr, G. Di Tullio, R. Weigert, D. Corda, M. A. De Matteis, & A. Luini. Role of NAD+ and ADP-ribosylation in the maintenance of the Golgi structure. (Submitted).
Weigert, R., A. Colanzi, C. Limina, C. Cericola, G. Di Tullio, A. Mironov, G. Santini, G. Sciulli, D. Corda, M. A. De Matteis, & A. Luini. 1996. Characterization of the endogenous mono ADP-ribosylation stimutated by brefeldin A. This book.
Weigert, R., A. Colanzi, G. Sciulli, A. Mironov, G. Santini, M. Di Girolamo, J. G. Donaldson, D. Corda, M. A. De Matteis, & A. Luini. Pharmacologic inhibitors of the brefeldin A-induced ADP-ribosylation. (Submitted).
Ma, Q., K. Cui, F. Xiao, A. Y. H. Lu, & C. S. Yang. 1992. Identification of a glycine-rich sequence as an NAD(P)H-binding site and tyrosine 128 as a dicumarol-binding site in rat liver NAD(P)H: quinone oxidoreductase by site-directed mutagenesis. J. Biol. Chem. 267: 22298–22304.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Colanzi, A. et al. (1997). Brefeldin A-Induced ADP-Ribosylation in the Structure and Function of the Golgi Complex. In: Haag, F., Koch-Nolte, F. (eds) ADP-Ribosylation in Animal Tissues. Advances in Experimental Medicine and Biology, vol 419. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8632-0_43
Download citation
DOI: https://doi.org/10.1007/978-1-4419-8632-0_43
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4652-4
Online ISBN: 978-1-4419-8632-0
eBook Packages: Springer Book Archive