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

Chivasso, Clara ; Hagströmer, Carl Johan LU orcid ; Rose, Kristie L. ; Lhotellerie, Florent ; Leblanc, Lionel ; Wang, Zhen ; Moscato, Stefania ; Chevalier, Clément ; Zindy, Egor and Martin, Maud , et al. (2021) In International Journal of Molecular Sciences 22(17).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aquaporin-5, Ezrin, Protein–protein interaction, Salivary glands, Sjögren’s syndrome
in
International Journal of Molecular Sciences
volume
22
issue
17
article number
9213
publisher
MDPI AG
external identifiers
  • scopus:85113484364
  • pmid:34502121
ISSN
1661-6596
DOI
10.3390/ijms22179213
language
English
LU publication?
yes
id
25b87584-ac63-4f07-be37-789949bc77a1
date added to LUP
2021-09-20 14:44:40
date last changed
2024-04-20 11:28:29
@article{25b87584-ac63-4f07-be37-789949bc77a1,
  abstract     = {{<p>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.</p>}},
  author       = {{Chivasso, Clara and Hagströmer, Carl Johan and Rose, Kristie L. and Lhotellerie, Florent and Leblanc, Lionel and Wang, Zhen and Moscato, Stefania and Chevalier, Clément and Zindy, Egor and Martin, Maud and Vanhollebeke, Benoit and Gregoire, Françoise and Bolaky, Nargis and Perret, Jason and Baldini, Chiara and Soyfoo, Muhammad Shahnawaz and Mattii, Letizia and Schey, Kevin L. and Törnroth-Horsefield, Susanna and Delporte, Christine}},
  issn         = {{1661-6596}},
  keywords     = {{Aquaporin-5; Ezrin; Protein–protein interaction; Salivary glands; Sjögren’s syndrome}},
  language     = {{eng}},
  number       = {{17}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Ezrin is a novel protein partner of aquaporin-5 in human salivary glands and shows altered expression and cellular localization in sjögren’s syndrome}},
  url          = {{http://dx.doi.org/10.3390/ijms22179213}},
  doi          = {{10.3390/ijms22179213}},
  volume       = {{22}},
  year         = {{2021}},
}