Effect of cholera toxin and cyclic adenosine monophosphate on fluid-phase endocytosis, distribution, and trafficking of endosomes in rat liver

In prior studies, we showed that cholera (CTX) and pertussis toxins (PTX) i ncrease rat liver endosome acidification. This study was performed to chara cterize the effects of these toxins and cyclic adenosine monophosphate (cAM P) on endosome ion transport, fluid-phase endocytosis (FPE), and endosome t rafficking in liver. In control liver, more mature populations of endosomes acidified progressively more slowly, but both toxins and cAMP caused reten tion of an early endosome acidification profile in maturing endosomes, CTX caused a density shift in endosomes, and all agents increased net FPE at ti me points from 5 to 60 minutes. By confocal microscopy, fluorescent dextran s first appeared in small vesicles at the hepatocyte sinusoidal membrane an d trafficked rapidly to the pericanalicular area, near lysosomes and the tr ans-Golgi network (TGN), Prolonged exposure to these agents caused redistri bution of many labeled vesicles to the perinuclear region, colocalized with markers of both early (EEA1 and transferrin receptor) and late (LAMP1) end osomes. We conclude that cAMP is the common agent that disrupted normal mat uration and trafficking of endosomes and increased net FPE, in part via dec reased diacytosis.