Phosphorylation of tight junction transmembrane proteins: Many sites, much to do

Abstract

Phosphorylation is a dynamic post-translational modification that can alter protein structure, localization, protein-protein interactions and stability. All of the identified tight junction transmembrane proteins can be multiply phosphorylated, but only in a few cases are the consequences of phosphorylation at specific sites well characterized. The goal of this review is to highlight some of the best understood examples of phosphorylation changes in the integral membrane tight junction proteins in the context of more general overview of the effects of phosphorylation throughout the proteome. We expect as that structural information for the tight junction proteins becomes more widely available and the molecular modeling algorithms improve, so will our understanding of the relevance of phosphorylation changes at single and multiple sites in tight junction proteins.

The Integral Role of Tight Junction Proteins in the Repair of Injured Intestinal Epithelium

“…Tight junctions are made up of a number of protein elements, including transmembrane claudins (total of 27 mammalian claudins), as well as myelin and lymphocyte (MAL) and related proteins for vesicle trafficking and membrane link (MARVEL) [13][14][15][16][17][18]. MARVEL domain-containing proteins are a component of a larger group of tight junction-associated MARVEL proteins (TAMPS) that include transmembrane proteins such as occludin and tricellulin [18][19][20]. Other tight junction-associated transmembrane molecules include junctional adhesion molecules (JAM-1, -2, and -3) that can regulate the formation of tight junctions and migration of neutrophils [21][22][23][24][25][26].…”

Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats

“…Posttranslational modification of tight junction proteins is responsible for tight junction function . ERK activation regulates the expression and distribution of tight junction proteins .…”

“…Loss of ZO‐1 disrupts claudins formation and localization and subsequently alters barrier function . Phosphorylation modification at the C‐terminus of claudins or occludin may affect protein interaction, distribution, and stability . Kale et al demonstrated that tyrosine phosphorylation of occludin disrupts its association with ZOs .…”

“…Posttranslational modification of tight junction proteins is responsible for tight junction function. 43,44 ERK activation regulates the expression and distribution of tight junction proteins. 45,46 Cong et al demonstrated that clau-4 is phosphorylated by ERK activation to trigger clau-4 internalization.…”

“…68,69 Phosphorylation modification at the C-terminus of claudins or occludin may affect protein interaction, distribution, and stability. 43 binds to extracellular domains and phosphorylated the cytoplasmic C-terminus of clau-4 to disturb the interaction between clau-4 and ZO-1. 71 Our data demonstrate that the association of clau-4 and ZO-1 was attenuated in MS rats, implying that phosphorylated clau-4 at serine sites may be resistant to interactions with ZO-1 and disrupted tight junction strand formation.…”