Phosphorylation of the polymeric immunoglobulin receptor required for its efficient transcytosis.
The endosomal compartment of polarized epithelial cells is a major crossroads for membrane traffic. Proteins entering this compartment from the cell surface are sorted for transport to one of several destinations: recycling to the original cell surface, targeting to lysosomes for degradation, or transcytosis to the opposite surface. The polymeric immunoglobulin receptor (pIgR), which is normally transcytosed from the basolateral to the apical surface, was used as a model to dissect the signals that mediate this sorting event. When exogenous receptor was expressed in Madin-Darby Canine Kidney (MDCK) cells, it was shown that phosphorylation of pIgR at the serine residue at position 664 is required for efficient transcytosis. Replacement of this serine with alanine generated a receptor that is transcytosed only slowly, and appears to be recycled. Conversely, substitution with aspartic acid (which mimics the negative charge of the phosphate group) results in rapid transcytosis. It was concluded that phosphorylation is the signal that directs the pIgR from the endosome into the transcytotic pathway.
Casanova
J E
JE
Department of Anatomy, University of California, San Francisco 94143.
Breitfeld
P P
PP
Ross
S A
SA
Mostov
K E
KE
D000409:Alanine; D000818:Animals; D001224:Aspartic Acid; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis; D007070:Immunoglobulin A / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D008970:Molecular Weight; D009154:Mutation; D010766:Phosphorylation; D051381:Rats; D011971:Receptors, Immunologic; D012635:Secretory Component / Q000235:genetics / Q000378:metabolism*; D012694:Serine
D007070:Immunoglobulin A; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D012635:Secretory Component; D001224:Aspartic Acid; D012694:Serine; D000409:Alanine