Altered distribution of aquaporin 5 and its C-terminal binding protein in the lacrimal glands of a mouse model for Sjögren's syndrome

Yoshiki Ohashi, Kensei Tsuzaka, Tsutomu Takeuchi, Yasumasa Sasaki, Kazuo Tsubota

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Purpose: To investigate the distribution and expression of aquaporin 5 (AQP5) and its C-terminal binding protein in the apical membrane of the lacrimal glands (LGs) in a mouse model for Sjogren's syndrome (SS). Methods: The LGs of NOD mice (mouse model for SS) and ICR mice (normal control) were homogenized and delivered into the affinity columns bound to synthetic AQP5 C-terminal peptide. The eluates were analyzed by electrophoresis and liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) techniques.Results: AQP5 from the NOD mice exhibited the capacity to bind a 21-kDa protein that was lacking in the ICR mice. Instead, ICR mouse expressed a 17-kDa AQP5 binding protein that was absent in LGs of SS. LC-MS/MS analysis revealed these respective proteins to be major urinary protein 4 (MUP4) and prolactin-inducible protein (PIP). The treatment of ICR mice with antisense PIP oligonucleotides decreased immunostaining of AQP5 in the apical membrane. Conclusions: These observations suggest that the binding of PIP to the C-terminal portion of AQP5 may cause AQP5 to be transported to the apical membrane of LGs. Correction of the aberrant binding of PIP to the AQP5 C-terminus could normalize AQP5 trafficking to the apical membrane, leading to a treatment for patients with SS.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalCurrent Eye Research
Volume33
Issue number8
DOIs
Publication statusPublished - 2008 Aug

Keywords

  • Aquaporin
  • Dry eye
  • Lacrimal gland
  • Prolactin-inducible protein
  • Sjogren's syndrome

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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