Dickinson*,Bonny L., Steven M. Claypool, June A. D'Angelo*,, Martha L. Aiken*,, Nanda Venu, Elizabeth H. Yen, Jessica S. Wagner,||, Jason A. Borawski, Amy T. Pierce*,, Robert Hershberg¶, Richard S. Blumberg,||, and Wayne I. Lencer||, 2008, Mol. Biol. Cell: 19:414-423.
*The Research Institute for Children, Children's Hospital, Department of Pediatrics, New Orleans, LA 70118; Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Science Center, New Orleans, LA 70112; Division of Gastroenterology, Brigham and Women's Hospital and the Department of Medicine, Harvard Medical School, Boston, MA 02115; Gastrointestinal Cell Biology, Division of Pediatric Gastroenterology and Nutrition, Children's Hospital and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115; ¶Department of Medicine and Medical Genetics, University of Washington School of Medicine, Seattle, WA 98112; and ||Harvard Digestive Diseases Center, Boston, MA 02115
Abstract
The Fc receptor FcRn transports immunoglobulin G (IgG) so as to avoid lysosomal degradation and to carry it bidirectionally across epithelial barriers to affect mucosal immunity. Here, we identify a calmodulin-binding site within the FcRn cytoplasmic tail that affects FcRn trafficking. Calmodulin binding to the FcRn tail is direct, calcium-dependent, reversible, and specific to residues comprising a putative short amphipathic -helix immediately adjacent to the membrane. FcRn mutants with single residue substitutions in this motif, or FcRn mutants lacking the cytoplasmic tail completely, exhibit a shorter half-life and attenuated transcytosis. Chemical inhibitors of calmodulin phenocopy the mutant FcRn defect in transcytosis. These results suggest a novel mechanism for regulation of IgG transport by calmodulin-dependent sorting of FcRn and its cargo away from a degradative pathway and into a bidirectional transcytotic route.
*Note: Normal Chicken IgY antibodies used in this publication were produced by Gallus Immunotech Inc. Please visit our Normal Chicken IgY page or see our Product Specifications for this product. | 
