Unraveling Human AQP5-PIP Molecular Interaction and Effect on AQP5 Salivary Glands Localization in SS Patients
Clara Chivasso,
Veronika Nesverova,
Michael Järvå,
Anne Blanchard,
Kristie L Rose,
Fredrik Kryh Öberg,
Zhen Wang,
Maud Martin,
Florent Lhotellerie,
Egor Zindy,
Bruna Junqueira,
Karelle Leroy,
Benoit Vanhollebeke,
Valérie Delforge,
Nargis Bolaky,
Jason Perret,
Muhammad Shahnawaz Soyfoo,
Stefania Moscato,
Chiara Baldini,
François Chaumont,
Letizia Mattii,
Kevin L Schey,
Yvonne Myal,
Susanna Törnroth-Horsefield,
Christine Delporte
Affiliations
Clara Chivasso
Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium
Veronika Nesverova
Division of Biochemistry and Structural Biology, Lund University, 221 00 Lund, Sweden
Michael Järvå
Department of Chemistry and Molecular Biology, University of Gothenburg, 907 36 Umeå, Sweden
Anne Blanchard
Department of Pathology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
Kristie L Rose
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37240, USA
Fredrik Kryh Öberg
Department of Chemistry and Molecular Biology, University of Gothenburg, 907 36 Umeå, Sweden
Zhen Wang
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37240, USA
Maud Martin
Laboratory of Neurovascular Signaling, Université Libre de Bruxelles, 6041 Gosselies, Belgium
Florent Lhotellerie
Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium
Egor Zindy
Multimodal Image Processing, Center for Microscopy and Molecular Imaging (CMMI), 6041 Gosselies, Belgium
Bruna Junqueira
Louvain Institute of Biomolecular Science and Technology, UCLouvain, 1348 Louvain-la Neuve, Belgium
Karelle Leroy
Laboratory of Histology, Neuroanatomy and Neuropathology, UNI (ULB Neuroscience Institute), Faculty of Medicine, Université Libre de Bruxelles, 1070 Brussels, Belgium
Benoit Vanhollebeke
Laboratory of Neurovascular Signaling, Université Libre de Bruxelles, 6041 Gosselies, Belgium
Valérie Delforge
Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium
Nargis Bolaky
Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium
Jason Perret
Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium
Muhammad Shahnawaz Soyfoo
Department of Rheumatology, Erasme Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium
Stefania Moscato
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Chiara Baldini
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
François Chaumont
Louvain Institute of Biomolecular Science and Technology, UCLouvain, 1348 Louvain-la Neuve, Belgium
Letizia Mattii
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
Kevin L Schey
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37240, USA
Yvonne Myal
Department of Pathology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
Susanna Törnroth-Horsefield
Division of Biochemistry and Structural Biology, Lund University, 221 00 Lund, Sweden
Christine Delporte
Laboratory of Pathophysiological and Nutritional Biochemistry, Université Libre de Bruxelles, 1070 Brussels, Belgium
Saliva secretion requires effective translocation of aquaporin 5 (AQP5) water channel to the salivary glands (SGs) acinar apical membrane. Patients with Sjögren’s syndrome (SS) display abnormal AQP5 localization within acinar cells from SGs that correlate with sicca manifestation and glands hypofunction. Several proteins such as Prolactin-inducible protein (PIP) may regulate AQP5 trafficking as observed in lacrimal glands from mice. However, the role of the AQP5-PIP complex remains poorly understood. In the present study, we show that PIP interacts with AQP5 in vitro and in mice as well as in human SGs and that PIP misexpression correlates with an altered AQP5 distribution at the acinar apical membrane in PIP knockout mice and SS hMSG. Furthermore, our data show that the protein-protein interaction involves the AQP5 C-terminus and the N-terminal of PIP (one molecule of PIP per AQP5 tetramer). In conclusion, our findings highlight for the first time the role of PIP as a protein controlling AQP5 localization in human salivary glands but extend beyond due to the PIP-AQP5 interaction described in lung and breast cancers.
