Crosstalk of tight junction components with signaling pathways

Abstract

Tight junctions (TJs) regulate the passage of ions and molecules through the paracellular pathway in epithelial and endothelial cells. TJs are highly dynamic structures whose degree of sealing varies according to external stimuli, physiological and pathological conditions. In this review we analyze how the crosstalk of protein kinase C, protein kinase A, myosin light chain kinase, mitogen-activated protein kinases, phosphoinositide 3-kinase and Rho signaling pathways is involved in TJ regulation triggered by diverse stimuli. We also report how the phosphorylation of the main TJ components, claudins, occludin and ZO proteins, impacts epithelial and endothelial cell function.

A Role for ZO-1 and PLEKHA7 in Recruiting Paracingulin to Tight and Adherens Junctions of Epithelial Cells

“…TJ and AJ carry out several functions: canonical roles in cell-cell adhesion and tissue sorting (AJ), cell polarization and permeability barrier functions (TJ), and signaling functions through pathways that control the organization of the cytoskeleton and the activity of transcription factors (for review, see Refs. [1][2][3][4][5][6][7][8][9][10]. All of these functions are orchestrated by complexes of transmembrane, cytoplasmic, and cytoskeletal proteins.…”

Irinotecan disrupts tight junction proteins within the gut

“…Briefly, peripherally located zonular occludens (ZO) proteins interact to anchor tight junction membrane proteins to the cytoskeleton. 13,14 These scaffolding proteins play important roles in tight junction formation and are crucial in barrier integrity. 13 Claudins are essential components of the intercellular tight junction and major determinants of paracellular solute fluxes.…”

“…13,14 These scaffolding proteins play important roles in tight junction formation and are crucial in barrier integrity. 13 Claudins are essential components of the intercellular tight junction and major determinants of paracellular solute fluxes. 15 The structural organization of claudin proteins varies and different claudin subtypes are responsible for different roles within the tight junction.…”

“…15 The structural organization of claudin proteins varies and different claudin subtypes are responsible for different roles within the tight junction. 13 Claudin-1 is of particular interest with regards to gastrointestinal inflammation and has been implicated in the pathophysiology of a number of inflammatory bowel disorders (IBDs). 16 Further, recent research has identified roles for claudin-1 in apoptosis 17 and cellular regeneration, 18 both of which are key events in CIGT.…”

“…13,19,20 For example, knockout (occludin −/− ) mice exhibit morphologically intact tight junctions, 21 however, poor tight junction integrity and mucosal barrier dysfunction follow. These results indicate likely roles for occludin in tight junction stability and barrier function as opposed to tight junction assembly.…”