Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Molecular biology of the cell, 2008-01, Vol.19 (1), p.414-423

Ort / Verlag

United States: The American Society for Cell Biology

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.