April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Tacstd2 Protein Directly Binds to Claudin Proteins and is Required for the Proper Subcellular Localization of Tight Junction-Related Proteins; Roles of Tacstd2 Protein in the Pathogenesis of Gelatinous Drop-Like Dystrophy
S. Kawasaki; M. Nakatsukasa; K. Yamasaki; H. Fukuoka; A. Matsuda; M. Tsujikawa; H. Tanioka; J. Hamuro; S. Kinoshita
Author Affiliations & Notes
  • S. Kawasaki
    Ophthalmology, Kyoto Prefectural Univ of Med, Kyoto, Japan
  • M. Nakatsukasa
    Ophthalmology, Kyoto Prefectural Univ of Med, Kyoto, Japan
  • K. Yamasaki
    Ophthalmology, Kyoto Prefectural Univ of Med, Kyoto, Japan
  • H. Fukuoka
    Ophthalmology, Kyoto Prefectural Univ of Med, Kyoto, Japan
  • A. Matsuda
    Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan
  • M. Tsujikawa
    Ophthalmology, Osaka University, Osaka, Japan
  • H. Tanioka
    Ophthalmology, Kyoto Prefectural Univ of Med, Kamigyo-ku, Japan
  • J. Hamuro
    Ophthalmology, Kyoto Prefectural Univ of Med, Kyoto, Japan
  • S. Kinoshita
    Ophthalmology, Kyoto Prefectural Univ of Med, Kamigyo-Ku, Japan
  • Footnotes
    Commercial Relationships  S. Kawasaki, None; M. Nakatsukasa, None; K. Yamasaki, None; H. Fukuoka, None; A. Matsuda, None; M. Tsujikawa, None; H. Tanioka, None; J. Hamuro, None; S. Kinoshita, None.
  • Footnotes
    Support  Japanese Grant 21592238
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4651. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      Tacstd2 Protein Directly Binds to Claudin Proteins and is Required for the Proper Subcellular Localization of Tight Junction-Related Proteins; Roles of Tacstd2 Protein in the Pathogenesis of Gelatinous Drop-Like Dystrophy
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      S. Kawasaki, M. Nakatsukasa, K. Yamasaki, H. Fukuoka, A. Matsuda, M. Tsujikawa, H. Tanioka, J. Hamuro, S. Kinoshita; Tacstd2 Protein Directly Binds to Claudin Proteins and is Required for the Proper Subcellular Localization of Tight Junction-Related Proteins; Roles of Tacstd2 Protein in the Pathogenesis of Gelatinous Drop-Like Dystrophy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4651.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

      ×
    • Get Permissions
  • Supplements
Abstract

Purpose: : Gelatinous drop-like dystrophy (GDLD) is a rare form of corneal dystrophy characterized by subepithelial amyloid depositions in the cornea with an autosomal recessive inheritance mode. From clinical and laboratory observations, it is strongly implied that epithelial barrier function is significantly decreased in this disease. Despite the decade-old identification of the tumor-associated calcium signal transducer 2 (TACSTD2) gene as a causative gene for GDLD, the mechanism is yet unknown by which the loss of function of this causative gene leads to the pathological consequence of GDLD. The purpose of this study was to elucidate the relationship between the TACSTD2 gene and epithelial barrier function.

Methods: : To investigate the protein-protein association between the TACSTD2 protein and tight junction (TJ)-related proteins, we performed immunoprecipitation (IP) and proximity ligation assay (PLA). Knockdown of the TACSTD2 gene in SV40-immortalized human corneal epithelial cells (HCE-T) was performed to investigate the role of the TACSTD2 protein in the epithelial barrier function and TJ formation. In addition, claudin genes were also knocked down to investigate their roles in the epithelial barrier function.

Results: : Through the use of IP and PLA, we obtained evidence that the TACSTD2 protein directly binds to claudin proteins. We also discovered that the ablated or decreased expression of the TACSTD2 gene leads to decreased expression and altered subcellular localization of claudin proteins, both in diseased cornea and HCE-T cells. In addition, decreased expression of the claudin genes resulted in a significant decrease in the epithelial barrier function of HCE-T cells.

Conclusions: : From these results, we conclude that loss of function of the TACSTD2 gene significantly diminishes epithelial barrier function through decreased expression and altered subcellular localization of tight junction-related proteins in GDLD corneas.

Keywords: cornea: epithelium • pump/barrier function • pathology: human 
© 2010, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept