Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1798, Issue 3, Pages 415-421Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2009.11.005
Keywords
Claudin-16; ERK; Phosphorylation
Categories
Funding
- Ministry of Education, Science, Sports, and Culture of Japan
- Salt Science Research Foundation [0830]
- Mochida Memorial Foundation
- Research Foundation for Pharmaceutical Sciences
- Grants-in-Aid for Scientific Research [21590170] Funding Source: KAKEN
Ask authors/readers for more resources
Claudin-16 is involved in the paracellular reabsorption of Me2+ in the thick ascending limb of Henle. Little is known about the mechanism regulating the tight junctional localization of claudin-16. Here, we examined the effect of Me2+ deprivation on the distribution and function of claudin-1 6 using Madin-Darby canine kidney (MDCK) cells expressing FLAG-tagged claudin-16. Me2+ deprivation inhibited the localization of claudin-1 6 at tight junctions, but did not affect the localization of other claudins. Re-addition of Me2+ induced the tight junctional localization of claudin-16, which was inhibited by U0126, a MEK inhibitor. Transepithelial permeability to Me2+ was also inhibited by U0126. The phosphorylation of ERK was reduced by Me2+ deprivation, and recovered by re-addition of Me2+. These results suggest that the MEK/ERK-dependent phosphorylation of claudin-16 affects the tight junctional localization and function of claudin-16. Mg2+ deprivation decreased the phosphothreonine levels of claudin-16. The phosphothreonine levels of T225A and T233A claudin-1 6 were decreased in the presence of Mg2+ and these mutants were widely distributed in the plasma membrane. Furthermore, TER and transepithelial Me2+ permeability were decreased in the mutants. We suggest that the tight junctional localization of claudin-1 6 requires a physiological Me2+ concentration and the phosphorylation of threonine residues via a MEK/ERK-dependent pathway. (C) 2009 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available