Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway

Bonny L. Dickinson, Steven M. Claypool, June A. D'Angelo, Martha L. Aiken, Nanda Venu, Elizabeth H. Yen, Jessica S. Wagner, Jason A. Borawski, Amy T. Pierce, Robert Hershberg, Richard S. Blumberg, Wayne I. Lencer

Research output: Contribution to journalArticle

Abstract

The Fcγ 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 α-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.

Original languageEnglish (US)
Pages (from-to)414-423
Number of pages10
JournalMolecular biology of the cell
Volume19
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Dickinson, B. L., Claypool, S. M., D'Angelo, J. A., Aiken, M. L., Venu, N., Yen, E. H., Wagner, J. S., Borawski, J. A., Pierce, A. T., Hershberg, R., Blumberg, R. S., & Lencer, W. I. (2008). Ca2+-dependent calmodulin binding to FcRn affects immunoglobulin G transport in the transcytotic pathway. Molecular biology of the cell, 19(1), 414-423. https://doi.org/10.1091/mbc.E07-07-0658