The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity.
The Fc receptor FcRn traffics immunoglobulin G (IgG) in both directions across polarized epithelial cells that line mucosal surfaces, contributing to host defense. We show that FcRn traffics IgG from either apical or basolateral membranes into the recycling endosome (RE), after which the actin motor myosin Vb and the GTPase Rab25 regulate a sorting step that specifies transcytosis without affecting recycling. Another regulatory component of the RE, Rab11a, is dispensable for transcytosis, but regulates recycling to the basolateral membrane only. None of these proteins affect FcRn trafficking away from lysosomes. Thus, FcRn transcytotic and recycling sorting steps are distinct. These results are consistent with a single structurally and functionally heterogeneous RE compartment that traffics FcRn to both cell surfaces while discriminating between recycling and transcytosis pathways polarized in their direction of transport.
Tzaban
Salit
S
Children's Hospital, Gastroenterology Division, Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115, USA.
Massol
Ramiro H
RH
Yen
Elizabeth
E
Hamman
Wendy
W
Frank
Scott R
SR
Lapierre
Lynne A
LA
Hansen
Steen H
SH
Goldenring
James R
JR
Blumberg
Richard S
RS
Lencer
Wayne I
WI
D000818:Animals; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D004285:Dogs; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000502:physiology; D024701:Myosin Type V / Q000502:physiology; D021381:Protein Transport; D011961:Receptors, Fc / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000502:physiology; D000099193:rab11 GTP-Binding Proteins
D007074:Immunoglobulin G; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D011961:Receptors, Fc; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C505832:MYO5B protein, human; C509763:Rab25 protein, human