Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway. Mol Biol Cell 2008 Jan;19(1):414-23
Date
11/16/2007Pubmed ID
18003977Pubmed Central ID
PMC2174181DOI
10.1091/mbc.e07-07-0658Scopus ID
2-s2.0-38749097778 (requires institutional sign-in at Scopus site) 51 CitationsAbstract
The Fcgamma 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 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 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.
Author List
Dickinson BL, Claypool SM, D'Angelo JA, Aiken ML, Venu N, Yen EH, Wagner JS, Borawski JA, Pierce AT, Hershberg R, Blumberg RS, Lencer WIMESH terms used to index this publication - Major topics in bold
Amino Acid MotifsAmino Acid Sequence
Animals
Calcium
Calmodulin
Cell Line
Cell Polarity
Dogs
Endocytosis
Half-Life
Histocompatibility Antigens Class I
Humans
Immunoglobulin G
Intestines
Lysosomes
Mice
Molecular Sequence Data
Protein Binding
Protein Structure, Tertiary
Protein Transport
Receptors, Fc
