RETROGRADE TRAFFICKING OF BOTH GOLGI-COMPLEX AND TGN MARKERS TO THE ER INDUCED BY NORDIHYDROGUAIARETIC ACID AND CYCLOFENIL DIPHENOL

Previous studies have shown that the Golgi stack and the trans-Golgi n etwork (TGN) may play a role in capturing escaped resident endoplasmic reticulum (ER) proteins, and directing their retrograde transport bac k to that organelle, Whether this retrograde movement represents a hig hly specific or more generalized membrane trafficking pathway is uncle ar. To better understand both the retrograde and anterograde trafficki ng pathways of the secretory apparatus, we examined more closely the i n vivo effects of two structurally unrelated compounds, the potent lip oxygenase inhibitor nordihydroguaiaretic acid (NDGA), and the non-ster oidal estrogen cyclofenil diphenol (CFD), both of which are known to i nhibit secretion, In the presence of these compounds, transport of ves icular stomatitis virus G membrane glycoprotein from the ER to the Gol gi complex, and from the TGN to the cell surface, was inhibited potent ly and rapidly. Surprisingly, we found that NDGA and CFD stimulated th e rapid, but not concomitant, retrograde movement of both Golgi stack and TGN membrane proteins back to the ER until both organelles were mo rphologically absent from cells. Both NDGA- and CFD-stimulated TGN and Golgi retrograde membrane trafficking were inhibited by microtubule d epolymerizing agents and energy poisons, Removal of NDGA and CFD resul ted in the complete, but not concomitant, reformation of both Golgi st acks and their closely associated TGN compartments. These studies sugg est that NDGA and CFD unmask a generalized bulk recycling pathway to t he ER for both Golgi and TGN membranes and, further, that NDGA and CFD are useful for investigating the molecular mechanisms that control th e formation and maintenance of both the Golgi stack proper and the TGN .