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Updated: Jul 10, 2026

Pull-down of Calmodulin-binding Proteins
Published on: January 23, 2012
Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway
Bonny L Dickinson1, Steven M Claypool, June A D'Angelo
1The Research Institute for Children, Children's Hospital, Department of Pediatrics, New Orleans, LA 70118, USA.
Abstract:
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.
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