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 tested the ability of ligand to promote receptor dimerization and the subsequent role of receptor dimerization on its intracellular trafficking. Using the cytoplasmic domain of the T cell receptor-zeta chain as a sensitive indicator of receptor oligomerization, we show that a pIgR:zeta chimeric receptor expressed in Jurkat cells initiates a zeta-specific signal transduction cascade when exposed to dimeric or tetrameric IgA, but not when exposed to monomeric IgA. In addition, we replaced the pIgR's transmembrane domain with that of glycophorin A to force dimerization or with a mutant glycophorin transmembrane domain to prevent dimerization. Forcing dimerization stimulated transcytosis of the chimera, whereas preventing dimerization abolished ligand-stimulated transcytosis. We conclude that binding of dimeric IgA to the pIgR induces its dimerization and that this dimerization is necessary and sufficient to stimulate pIgR transcytosis.
Singer
K L
KL
Department of Anatomy and Department of Biochemistry and Biophysics, and Cardiovascular Research Institute, University of California, San Francisco, California 94143-0452, USA.
Mostov
K E
KE
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004285:Dogs; D006021:Glycophorins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry / Q000378:metabolism; D007457:Iodine Radioisotopes; D019169:Jurkat Cells / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D011961:Receptors, Fc / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D006021:Glycophorins; C045281:IgA receptor; D007070:Immunoglobulin A; D007457:Iodine Radioisotopes; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D011994:Recombinant Proteins