Transcytosis of the polymeric immunoglobulin receptor is regulated in multiple intracellular compartments.

Transcytosis of the polymeric immunoglobulin receptor (pIgR) can be experimentally divided into three steps: 1) internalization from the basolateral plasma membrane and delivery to basolateral early endosomes, 2) microtubule-dependent movement from basolateral early endosomes to apical recycling endosomes, and 3) delivery from apical recycling endosomes to the apical surface and cleavage of the pIgR to secretory component, which is released into the apical medium. Transcytosis of the pIgR is stimulated by two signals, phosphorylation of Ser-664 in the cytoplasmic domain of the pIgR and binding of the ligand, dimeric IgA, to the pIgR. These signals do not detectably alter step 1 of transcytosis. Here, we show that phosphorylation of Ser-664 stimulates both steps 2 and 3, whereas binding of dimeric IgA stimulates only step 3 of transcytosis.