Ezrin is a novel protein partner of aquaporin-5 in human salivary glands and shows altered expression and cellular localization in sjögren’s syndrome

Clara Chivasso, Carl Johan Hagströmer, Kristie L. Rose, Florent Lhotellerie, Lionel Leblanc, Zhen Wang, Stefania Moscato, Clément Chevalier, Egor Zindy, Maud Martin, Benoit Vanhollebeke, Françoise Gregoire, Nargis Bolaky, Jason Perret, Chiara Baldini, Muhammad Shahnawaz Soyfoo, Letizia Mattii, Kevin L. Schey, Susanna Törnroth-Horsefield, Christine Delporte

Research output: Contribution to journalArticlepeer-review

Abstract

Sjögren’s syndrome (SS) is an exocrinopathy characterized by the hypofunction of salivary glands (SGs). Aquaporin-5 (AQP5); a water channel involved in saliva formation; is aberrantly dis-tributed in SS SG acini and contributes to glandular dysfunction. We aimed to investigate the role of ezrin in AQP5 mislocalization in SS SGs. The AQP5–ezrin interaction was assessed by immuno-precipitation and proteome analysis and by proximity ligation assay in immortalized human SG cells. We demonstrated, for the first time, an interaction between ezrin and AQP5. A model of the complex was derived by computer modeling and in silico docking; suggesting that AQP5 interacts with the ezrin FERM-domain via its C-terminus. The interaction was also investigated in human minor salivary gland (hMSG) acini from SS patients (SICCA-SS); showing that AQP5–ezrin complexes were absent or mislocalized to the basolateral side of SG acini rather than the apical region compared to controls (SICCA-NS). Furthermore, in SICCA-SS hMSG acinar cells, ezrin immunore-activity was decreased at the acinar apical region and higher at basal or lateral regions, accounting for altered AQP5–ezrin co-localization. Our data reveal that AQP5–ezrin interactions in human SGs could be involved in the regulation of AQP5 trafficking and may contribute to AQP5-altered localization in SS patients.

Original languageEnglish
Article number9213
JournalInternational Journal of Molecular Sciences
Volume22
Issue number17
DOIs
Publication statusPublished - 2021 Sep

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity
  • Cell and Molecular Biology

Keywords

  • Aquaporin-5
  • Ezrin
  • Protein–protein interaction
  • Salivary glands
  • Sjögren’s syndrome

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