IgG transcytosis and recycling by FcRn expressed in MDCK cells reveals ligand-induced redistribution.
The neonatal Fc receptor (FcRn) transports IgG across epithelial cells and recycles serum IgG. FcRn binds IgG at the acidic pH of endosomes and releases IgG at the basic pH of blood. We expressed rat FcRn in polarized MDCK cells and demonstrated that it functions in transcytosis and recycling of IgG. In the absence of IgG, FcRn is distributed predominantly apically, but redistributes to basolateral locations upon IgG addition, indicating that ligand binding induces a signal that stimulates transcytosis. FcRn transcytoses IgG more efficiently in the apical to basolateral than the reverse direction when IgG is internalized by receptor-mediated endocytosis at acidic pH or by fluid phase endocytosis at basic pH. The PI 3-kinase inhibitor wortmannin disrupts basolateral recycling and transcytosis in both directions, but only minimally reduces apical recycling. Confocal imaging and quantitative IgG transport studies demonstrate that apically-internalized IgG recycles to the apical surface mainly from wortmannin-insensitive apical early endosomes, whereas FcRn-IgG complexes that transcytose to the basolateral surface pass through downstream Rab11-positive apical recycling endosomes and transferrin-positive common endosomal compartments.
Ramalingam
T S
TS
Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
Detmer
Scott A
SA
Martin
W Lance
WL
Bjorkman
Pamela J
PJ
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002451:Cell Compartmentation; D002460:Cell Line; D004285:Dogs; D004705:Endocytosis; D049452:Green Fluorescent Proteins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G / Q000378:metabolism*; D008024:Ligands; D008164:Luminescent Proteins / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D008164:Luminescent Proteins; D011961:Receptors, Fc; D049452:Green Fluorescent Proteins; D015739:Nocodazole; C100688:Fc receptor, neonatal; D000077191:Wortmannin