Mechanisms involved in AMPK-mediated deposition of tight junction components to the plasma membrane.

[en] AMP activated protein kinase (AMPK) activation promotes early stages of epithelial junction assembly. AMPK activation in MDCK renal epithelial cells facilitates localization of the junction-associated proteins aPKCzeta and Par3 to the plasma membrane and promotes conversion of Cdc42, a key regulator of epithelial polarization and junction assembly, to its active GTP bound state. Furthermore, Par3 is an important regulator of AMPK-mediated aPKCzeta localization. Both aPKCzeta and Par3 serve as intermediates in AMPK-mediated junction assembly, with inhibition of aPKCzeta activity or Par3 knockdown disrupting AMPK's ability to facilitate zonula occludens (ZO-1) localization. AMPK phosphorylates the adherens junction protein afadin and regulates its interaction with the tight junction protein zonula occludens (ZO)-1. Afadin is phosphorylated at two critical sites, S182 (residing within an aPKCzeta consensus site) and S1049 (residing within an AMPK consensus site), that are differentially regulated during junction assembly and that exert different effects on the process. Expression of phospho-defective mutants (S182A and S1082A) perturbed ZO-1 localization to the plasma membrane during AMPK-induced junction assembly. Expression of S182A increased the ZO-1/afadin interaction, while S1049A reduced this interaction during extracellular calcium-induced junction assembly. Inhibition of aPKCzeta activity also increased the ZO-1/afadin interaction. Taken together, these data suggest that aPKCzeta phosphorylation of afadin terminates the ZO-1/afadin interaction, and thus permits the later stages of junction assembly.

Disciplines :

Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Wu, Jingshing

Rowart, Pascal

Jouret, François ; Université de Liège - ULiège > Cardiovascular Sc.-Lab. of Translational Res. in Nephrology

Gassaway, Brandon M.

Rajendran, Vanathy

Rinehart, Jesse

Caplan, Michael J.

Language :

English

Title :

Mechanisms involved in AMPK-mediated deposition of tight junction components to the plasma membrane.

Publication date :

2020

Journal title :

American Journal of Physiology - Cell Physiology

ISSN :

0363-6143

eISSN :

1522-1563

Publisher :

American Physiological Society, United States - Maryland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 21 January 2020

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