Implications of AMPK in the Formation of Epithelial Tight Junctions

Tight junctions (TJ) play an essential role in the epithelial barrier. By definition, TJ are located at the demarcation between the apical and baso-lateral domains of the plasma membrane in epithelial cells. TJ fulfill two major roles: (i) TJ prevent the mixing of membrane components; and (ii) TJ regulate the selective paracellular permeability. Disruption of TJ is regarded as one of the earliest hallmarks of epithelial injury, leading to the loss of cell polarity and tissue disorganization. Many factors have been identified as modulators of TJ assembly/disassembly. More specifically, in addition to its role as an energy sensor, adenosine monophosphate-activated protein kinase (AMPK) participates in TJ regulation. AMPK is a ubiquitous serine/threonine kinase composed of a catalytic alpha-subunit complexed with regulatory beta- and gamma-subunits. AMPK activation promotes the early stages of epithelial TJ assembly. AMPK phosphorylates the adherens junction protein afadin and regulates its interaction with the TJ-associated protein zonula occludens (ZO)-1, thereby facilitating ZO-1 distribution to the plasma membrane. In the present review, we detail the signaling pathways up-and down-stream of AMPK activation at the time of Ca2+-induced TJ assembly.