TRANSCYTOSIS OF CHOLERA-TOXIN SUBUNITS ACROSS MODEL HUMAN INTESTINAL EPITHELIA

Cholera toxin (CT) elicits a massive secretory response from intestina l epithelia by binding apical receptors (ganglioside G(M1)) and ultima tely activating basolateral effecters (adenylate cyclase). The mechani sm of signal transduction from apical to basolateral membrane, however , remains undefined. We have previously shown that CT action on the po larized human intestinal epithelial cell line T84 requires endocytosis and processing in multiple intracellular compartments. Our aim in the present study was to test the hypothesis that CT may actually move to its site of action on the basolateral membrane by vesicular traffic. After binding apical receptors, CT entered basolaterally directed tran scytotic vesicles. Both CT B subunits and to a lesser extent CT A subu nits were delivered intact to the serosal surface of the basolateral m embrane, The toxin did not traverse the monolayer by diffusion through intercellular junctions. Transcytosis of CT B subunits displayed near ly identical time course and temperature dependency with that of CT-in duced Cl- secretion-suggesting the two may be related. These data iden tify a mechanism that may explain the link between the toxin's apical receptor and basolateral effector.