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J. Biol. Chem., Vol. 266, Issue 28, 18443-18445, Oct, 1991
M Zizi, RS Fisher and FG Grillo
Brefeldin A (BFA) is a novel agent with the unique property of effecting a
rapid increase of Golgi cisternae volume and subsequent loss of a
recognizable Golgi apparatus in treated cells. Although a receptor-mediated
mechanism has been proposed, the molecular basis of BFA action remains
unknown (Lippincott-Schwartz, J., Glickman, J., Donaldson, J. G., Robbins,
J., Kreis, T. E., Seamon, K. B., Sheetz, M. P., and Klausner, R. D. (1991)
J. Cell Biol. 112, 567-577). Since a variety of ionophores distort Golgi
architecture by initially causing osmotic swelling of the cisternae
(Mollenhauer, H. H., Morre, D. J., and Rowe, L. D. (1990) Biochim. Biophys.
Acta 1031, 225-246), Golgi membrane permeabilization by BFA seemed
possible. We examined the effects of BFA on the conductance of planar lipid
bilayers bathed in several aqueous salt solutions. Addition of BFA (1
microgram/ml) quickly augmented alkali cation conductance (K+ greater than
Na+ much greater than Li+) but not anion conductance of the bilayer. Lower
concentrations (1 ng/ml) indicated that BFA formed discrete, cation-
selective channels in these bilayers. Given that Golgi cisternae volume
increases immediately upon treatment with BFA, these findings suggest that
alteration of ion gradients or Golgi membrane potential followed by an
influx of water may be the mechanism by which BFA initiates disruption of
Golgi structural integrity. Subsequent functional perturbations may then
ensue either as a consequence of these initial structural changes or by a
combination of several distinct mechanisms.
Formation of cation channels in planar lipid bilayers by brefeldin A
Department of Nephrology, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
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