Transduction of basolateral-to-apical signals across epithelial cells: ligand-stimulated transcytosis of the polymeric immunoglobulin receptor requires two signals.
Transcytosis of the polymeric immunoglobulin receptor (pIgR) is stimulated by binding of its ligand, dimeric IgA (dIgA). During this process, dIgA binding at the basolateral surface of the epithelial cell transmits a signal to the apical region of the cell, which in turn stimulates the transport of dIgA-pIgR complex from a postmicrotubule compartment to the apical surface. We have previously reported that the signal of stimulation was controlled by a protein-tyrosine kinase (PTK) activated upon dIgA binding. We now show that this signal of stimulation moves across the cell independently of pIgR movement or microtubules and acts through the tyrosine kinase activity by releasing Ca++ from inositol trisphosphate-sensitive intracellular stores. Surprisingly we have found that a second independent signal is required to achieve dIgA-stimulated transcytosis of pIgR. This second signal depends on dIgA binding to the pIgR solely at the basolateral surface and the ability of pIgR to dimerize. This enables pIgR molecules that have bound dIgA at the basolateral surface to respond to the signal of stimulation once they reach the postmicrotubule compartment. We propose that the use of two signals may be a general mechanism by which signaling receptors maintain specificity along their signaling and trafficking pathways.
Luton
F
F
Departments of Anatomy and Biochemistry and Cardiovascular Research Institute, University of California, San Francisco, California 94143-0452, USA.
Mostov
K E
KE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002451:Cell Compartmentation; D002460:Cell Line; D019281:Dimerization; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005816:Genetic Complementation Test; D007070:Immunoglobulin A / Q000378:metabolism / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D007070:Immunoglobulin A; D019056:Receptors, Polymeric Immunoglobulin; D011505:Protein-Tyrosine Kinases; D002118:Calcium