Administration	Basic Sciences	Clinical Sciences	Centers of Excellence
Admissions Alumni Affairs Community and Minority Health Education Computer Support Continuing Education Dean's Office Faculty & Institutional Affairs Fiscal Affairs Libraries Medical Education Research Student Affairs	Biochemistry & Molecular Biology Cell Biology & Anatomy Genetics Microbiology, Immunology & Parasitology Pharmacology Physiology	Anesthesiology Dermatology Family Medicine Internal Medicine Emergency Medicine Gastroenterology Physical Medicine & Rehabilitation Neurology Neurosurgery OB/GYN Ophthalmology Orthopaedics Otorhinolaryngology Pathology Pediatrics Psychiatry Radiology Surgery Urology	Alcohol and Drug Abuse Center Cardiovascular Center Center for Molecular and Human Genetics Epilepsy Center Eye Center Ernest N. Morial Asthma, Allergy, and Respiratory Disease Center Gene Therapy Program Low Vision Center Neurosciences Center The Research Institute For Children Stanley S. Scott Cancer Center

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