The endoplasmic reticulum resident protein AGR3: Required for regulation of ciliary beat frequency in the airway

Luke R. Bonser, Bradley W. Schroeder, Lisa A. Ostrin, Nathalie Baumlin, Jean L. Olson, Matthias A Salathe, David J. Erle

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Protein disulfide isomerase (PDI) family members regulate protein folding and calcium homeostasis in the endoplasmic reticulum (ER). The PDI family member anterior gradient (AGR) 3 is expressed in the airway, but the localization, regulation, and function of AGR3 are poorly understood. Here we report that AGR3, unlike its closest homolog AGR2, is restricted to ciliated cells in the airway epithelium and is not induced by ER stress. Mice lacking AGR3 are viable and develop ciliated cells with normal-appearing cilia. However, ciliary beat frequency was lower in airways from AGR3-deficient mice compared with control mice (20% lower in the absence of stimulation and 35% lower after ATP stimulation). AGR3 deficiency had no detectable effects on ciliary beat frequency (CBF) when airways were perfused with a calcium-free solution, suggesting that AGR3 is required for calcium-mediated regulation of ciliary function. Decreased CBF was associated with impaired mucociliary clearance in AGR3-deficient airways. We conclude that AGR3 is a specialized member of the PDI family that plays an unexpected role in the regulation of CBF and mucociliary clearance in the airway.

Original languageEnglish (US)
Pages (from-to)536-543
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume53
Issue number4
DOIs
StatePublished - Oct 1 2015

Keywords

  • AGR2
  • AGR3
  • Ciliary beat frequency
  • Mucociliary clearance
  • Protein disulfide isomerase

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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