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Reciprocal Association between the Apical Junctional Complex and AMPK: A Promising Therapeutic Target for Epithelial/Endothelial Barrier Function?

1
Laboratory of Biological Science, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0811, Japan
2
Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
3
Laboratory of Biological Science, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0811, Japan
4
Strategic Innovation and Research Center, Teikyo University, Tokyo 173-8605, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6012; https://doi.org/10.3390/ijms20236012
Received: 8 November 2019 / Revised: 26 November 2019 / Accepted: 26 November 2019 / Published: 29 November 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Epithelial/endothelial cells adhere to each other via cell–cell junctions including tight junctions (TJs) and adherens junctions (AJs). TJs and AJs are spatiotemporally and functionally integrated, and are thus often collectively defined as apical junctional complexes (AJCs), regulating a number of spatiotemporal events including paracellular barrier, selective permeability, apicobasal cell polarity, mechano-sensing, intracellular signaling cascades, and epithelial morphogenesis. Over the past 15 years, it has been acknowledged that adenosine monophosphate (AMP)-activated protein kinase (AMPK), a well-known central regulator of energy metabolism, has a reciprocal association with AJCs. Here, we review the current knowledge of this association and show the following evidences: (1) as an upstream regulator, AJs activate the liver kinase B1 (LKB1)–AMPK axis particularly in response to applied junctional tension, and (2) TJ function and apicobasal cell polarization are downstream targets of AMPK and are promoted by AMPK activation. Although molecular mechanisms underlying these phenomena have not yet been completely elucidated, identifications of novel AMPK effectors in AJCs and AMPK-driven epithelial transcription factors have enhanced our knowledge. More intensive studies along this line would eventually lead to the development of AMPK-based therapies, enabling us to manipulate epithelial/endothelial barrier function. View Full-Text
Keywords: tight junction; adherens junction; apical junctional complex; AMP-activated protein kinase (AMPK); paracellular barrier tight junction; adherens junction; apical junctional complex; AMP-activated protein kinase (AMPK); paracellular barrier
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MDPI and ACS Style

Tsukita, K.; Yano, T.; Tamura, A.; Tsukita, S. Reciprocal Association between the Apical Junctional Complex and AMPK: A Promising Therapeutic Target for Epithelial/Endothelial Barrier Function? Int. J. Mol. Sci. 2019, 20, 6012. https://doi.org/10.3390/ijms20236012

AMA Style

Tsukita K, Yano T, Tamura A, Tsukita S. Reciprocal Association between the Apical Junctional Complex and AMPK: A Promising Therapeutic Target for Epithelial/Endothelial Barrier Function? International Journal of Molecular Sciences. 2019; 20(23):6012. https://doi.org/10.3390/ijms20236012

Chicago/Turabian Style

Tsukita, Kazuto; Yano, Tomoki; Tamura, Atsushi; Tsukita, Sachiko. 2019. "Reciprocal Association between the Apical Junctional Complex and AMPK: A Promising Therapeutic Target for Epithelial/Endothelial Barrier Function?" Int. J. Mol. Sci. 20, no. 23: 6012. https://doi.org/10.3390/ijms20236012

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