POLARIZED SORTING OF THE POLYMERIC IMMUNOGLOBULIN RECEPTOR IN THE EXOCYTOTIC AND ENDOCYTOTIC PATHWAYS IS CONTROLLED BY THE SAME AMINO-ACIDS

Polarized epithelial cells can sort plasma membrane proteins to the ap ical or basolateral domain either by direct targeting from the trans-G olgi network (TGN) or by targeting to one surface, followed by endocyt osis and transcytosis to the opposite surface. In Madin-Darby canine k idney (MDCK) cells, targeting of the polymeric immunoglobulin receptor (pIgR) to the basolateral surface is controlled by a sorting signal r esiding in the membrane proximal 17 amino acids of the cytoplasmic dom ain of this receptor. We have recently found that individual mutations at any of three residues in this signal, His656, Arg657 and Val660, s ubstantially decrease targeting from the TGN to the basolateral surfac e and correspondingly increase targeting from the TGN to the apical su rface. Here we report that these mutations decrease the recycling of b asolaterally endocytosed pIgR to that surface, and correspondingly inc rease its transcytosis to the apical surface. This effect occurred in mutant pIgRs that either contained the full-length cytoplasmic domain or were truncated to contain only the 17-residue basolateral targeting signal, and was independent of phosphorylation of pIgR at Ser664. Our results indicate that polarized sorting of the pIgR in the endocytoti c and exocytotic pathways are controlled by the same amino acids.