Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor.
The human MHC class I-related neonatal Fc receptor, hFcRn, mediates bidirectional transport of IgG across mucosal barriers. Here, we find that at steady state hFcRn distributes predominantly to an apical intracellular compartment and almost exclusively to the basolateral cell surface of polarized epithelial cells. It moves only transiently to the apical membrane. Ligand binding does not redistribute the steady state location of the receptor. Removal of the cytoplasmic tail that contains di-leucine and tryptophan-based endocytosis motifs or incubation at low temperature (18 degrees C) redistributes the receptor apically. The rates of endocytosis of the full-length hFcRn from the apical or basolateral membrane domains, however, are equal. Thus, the strong cell surface polarity displayed by hFcRn results from dominant basolateral sorting by motifs in the cytoplasmic tail that nonetheless allows for a cycle of bidirectional transcytosis.
Claypool
Steven M
SM
Harvard Medical School, Program in Immunology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Dickinson
Bonny L
BL
Wagner
Jessica S
JS
Johansen
Finn-Eirik
FE
Venu
Nanda
N
Borawski
Jason A
JA
Lencer
Wayne I
WI
Blumberg
Richard S
RS
D000818:Animals; D001692:Biological Transport; D019921:Biotinylation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D004705:Endocytosis; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D015395:Histocompatibility Antigens Class I; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D007150:Immunohistochemistry; D007930:Leucine / Q000737:chemistry; D008024:Ligands; D018613:Microscopy, Confocal; D010957:Plasmids / Q000378:metabolism; D011961:Receptors, Fc / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014162:Transfection; D014364:Tryptophan / Q000737:chemistry
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D011961:Receptors, Fc; D011994:Recombinant Proteins; D014364:Tryptophan; D007930:Leucine; C100688:Fc receptor, neonatal