CaMKII regulates the strength of the epithelial barrier.
Epithelial cells define the boundary between the outside and the inside of our body by constructing the diffusion barrier. Tight junctions (TJs) of epithelial cells function as barriers against invasion of harmful microorganisms into the human body and free diffusion of water or ions from the body. Therefore, formation of TJs has to be strictly controlled in epithelial cells. However, the molecular mechanisms governing this regulation are largely unknown. In this study, we identified Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) as a regulator of the barrier function of TJs. CaMKII inhibition led to enlargement of TJ-areas and up-regulation of the barrier function. CaMKII inhibition induced excess TJ formation in part by the activation of AMP-activated protein kinase (AMPK) and subsequent phosphorylation of claudin-1. As up-regulation of epithelial barriers is essential for the prevention of chronic inflammatory diseases, the identification of CaMKII as a modulator of TJ function paves the way for the development of new drugs to treat these diseases.
Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Ryo
R
Shiomi
Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Kenta
K
Shigetomi
Department of Morphological Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
Tetsuichiro
T
Inai
Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
Masami
M
Sakai
1] Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan [2] PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Junichi
J
Ikenouchi
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D062445:Claudin-1 / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology*
D062445:Claudin-1; C568113:Cldn1 protein, mouse; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D055372:AMP-Activated Protein Kinases