Signal transduction by the polymeric immunoglobulin receptor suggests a role in regulation of receptor transcytosis.
Many membrane traffic events that were previously thought to be constitutive recently have been found to be regulated by a variety of intracellular signaling pathways. The polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA (dIgA) from the basolateral to the apical surface of polarized epithelial cells. Transcytosis is stimulated by binding of dIgA to the pIgR, indicating that the pIgR can transduce a signal to the cytoplasmic machinery responsible for membrane traffic. We report that dIgA binding to the pIgR causes activation of protein kinase C (PKC) and release of inositol 1,4,5-trisphosphate (IP3). The IP3 causes an elevation of intracellular Ca. Artificially activating PKC with phorbol myristate acetate or poisoning the calcium pump with thapsigargin stimulates transcytosis of pIgR, while the intracellular Ca chelator BAPTA-AM inhibits transcytosis. Our data suggest that ligand-induced signaling by the pIgR may regulate membrane traffic via well-known second messenger pathways involving PKC, IP3, and Ca. This may be a model of a general means by which membrane traffic is regulated by receptor-ligand interaction and signaling pathways.
Cardone
M H
MH
Department of Anatomy, University of California, San Francisco, 94143-0452, USA.
Smith
B L
BL
Mennitt
P A
PA
Mochly-Rosen
D
D
Silver
R B
RB
Mostov
K E
KE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004285:Dogs; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D007070:Immunoglobulin A / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000378:metabolism*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007070:Immunoglobulin A; D019056:Receptors, Polymeric Immunoglobulin; D013729:Terpenes; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium