Brefeldin A (BFA) disrupts the organization of the microtubule and actin cytoeskeletons.

ALVAREZ, C; SZTUL, E

EUROPEAN JOURNAL OF CELL BIOLOGY

ELSEVIER GMBH

Año: 1999 vol. 78 p. 1 - 14

0171-9335

Previous inquiries into the effects of Brefeldin A (BFA) have largely concentrated on dynamics of ER-Golgi membrane traffic, predominantly after relatively short treatments with the drug. We have now analyzed the effects of long BFA treatment on overall cell morphology, behavior of resident and cycling Golgi proteins, and microtnbular and actin cytoskeletons organization. Prolonged (ISh or 4Oh) treatment of normal rat kidney (NRK) cells with BFA caused dramatic swelling of the Endoplasmic Reticulum (ER) and shifted its localization to the periphery of the cells. The Golgi complex was disassembled and Golgiproteins redistributed and persisted in partially distinct compartments.Prolonged BFA treatment resulted in marked disruption of the MT and actin cytoskeleton. Peripheral MT were absent and tubulin staining was concentrated in short astral MT emanating from the microtubule organizing center (MTOC). Actin stress fibers were largely absent and actin staining was concentrated within a perinuclear area. Within this region, actin localization overlapped that of the membran transport factor pUS. BFA effects on Golgi structure and on MT and actin organization showed the same threshold - all could be partially reversed after 30min and ISh BFA treatment but were irreversible after 40 h incubation with the drug. The observed effects were not induced by signaling pathways involved in apoptotic phenomena or in ER stress response pathways. These results suggest that BFA inhibits the activity of key molecules that regulate MT and actin cytoskeletondynamics. The frndings can be used as the basis for elucidating the molecular mechanism of BFA action on the cytoskeleton.