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The Fc-gamma receptor, FcRn, functions to transport IgG across epithelial barriers.

Principal Investigator: Bonny L. Dickinson, Ph.D.

Abstract

The Fc-gamma receptor FcRn binds and traffics IgG so as to prolong IgG the serum half-life of the molecule and to carry IgG bi-directionally across epithelial cellsepithelial barriers to affect mucosal immunity. How the receptor sorts IgG through the cell to accomplish these functions remains unknown. We have identified a calmodulin-binding site within the FcRn cytoplasmic tail that affects FcRn trafficking in polarized epithelial cells. Calmodulin binding to the FcRn tail is direct, calcium-dependent, reversible, and specific to residues comprising a putative,short amphipathic alpha-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 transport IgG less efficiently across model epithelial barriers. These results suggest a mechanism for the regulation ofIgG transepithelial transport by calmodulin-dependent sorting of FcRn and its cargo away from a degradative pathway and into a transcytotic route. We are interested in defining a role for FcRn in the development or perpetuation of inflammatory bowel disease.

Sponsor: The Crohn’s and Colitis Foundation of America