Dickinson, Bonny L.Claypool, Steven M.D'Angelo, June A.Aiken, Martha L.Venu, NandaYen, Elizabeth H.Wagner, Jessica S.Borawski, Jason A.Pierce, Amy T.Hershberg, RobertBlumberg, Richard S.Lencer, Wayne I.2019-10-052008Dickinson, Bonny L., Steven M. Claypool, June A. D’Angelo, Martha L. Aiken, Nanda Venu, Elizabeth H. Yen, Jessica S. Wagner, et al. 2008. “Ca2+-Dependent Calmodulin Binding to FcRn Affects Immunoglobulin G Transport in the Transcytotic Pathway.” Edited by Keith Mostov. Molecular Biology of the Cell 19 (1): 414–23. https://doi.org/10.1091/mbc.e07-07-0658.1059-15241939-4586http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483357The Fc gamma 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.en-USJournal Article2019-10-0510.1091/mbc.E07-07-0658