DIMERIZATION OF THE POLYMERIC IMMUNOGLOBULIN RECEPTOR CONTROLS ITS TRANSCYTOTIC TRAFFICKING

Binding of dimeric immunoglobulin (Ig)A to the polymeric Ig receptor ( pIgR) stimulates transcytosis of pIgR across epithelial cells. Through the generation of a series of pIgR chimeric constructs, we have teste d the ability of ligand to promote receptor dimerization and the subse quent role of receptor dimerization on its intracellular trafficking. Using the cytoplasmic domain of the T cell receptor-zeta chain as a se nsitive indicator of receptor oligomerization, we show that a pIgR:zet a chimeric receptor expressed in Jurkat cells initiates a zeta-specifi c signal transduction cascade when exposed to dimeric or tetrameric Ig A, but not when exposed to monomeric IgA. In addition, we replaced the pIgR's transmembrane domain with that of glycophorin A to force dimer ization or With a mutant glycophorin transmembrane domain to prevent d imerization. Forcing dimerization stimulated transcytosis of the chime ra, whereas preventing dimerization abolished ligand-stimulated transc ytosis. We conclude that binding of dimeric IgA to the pIgR induces it s dimerization and that this dimerization is necessary and sufficient to stimulate pIgR transcytosis.