Scaffolding proteins of vertebrate apical junctions: structure, functions and biophysics

• Published in: Biochimica et biophysica acta. Biomembranes Vol. 1862; no. 10; p. 183399
• Main Authors: Rouaud, Florian, Sluysmans, Sophie, Flinois, Arielle, Shah, Jimit, Vasileva, Ekaterina, Citi, Sandra
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2020
• Subjects: Adherens junction; Afadin; Angiomotin; Animals; Biophysical Phenomena; Cingulin; Cytoplasm - metabolism; Intercellular Junctions - metabolism; Ligands; MAGI; Pals1; Par3; Par6; Paracingulin; PATJ; PLEKHA7; Tight junction; Vertebrates - metabolism; ZO-1; PATJ; Angiomotin; Pals1; PLEKHA7; Adherens junction; Cingulin; Par6; ZO-1; MAGI; Par3; Afadin; Tight junction; Paracingulin
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2020.183399

Tight and adherens junctions are specialized sites of cell-cell interaction in epithelia and endothelia, and are involved in barrier, adhesion, and signaling functions. These functions are orchestrated by a highly organized meshwork of macromolecules in the membrane and cytoplasmic compartments. In this review, we discuss the structural organization and functions of the major cytoplasmic scaffolding and adaptor proteins of vertebrate apical junctions (ZO proteins, afadin, PLEKHA7, cingulin, paracingulin, polarity complex proteins, and a few others), focusing on their interactions with cytoskeletal and signaling proteins. Furthermore, we discuss recent results highlighting how mechanical tension, protein-protein interactions and post-translational modifications regulate the conformation and function of scaffolding proteins, and how spontaneous phase separation into biomolecular condensates contributes to apical junction assembly. Using a sequence-based algorithm, a large fraction of cytoplasmic proteins of apical junctions are predicted to be phase separating proteins (PSPs), suggesting that formation of biomolecular condensates is a general mechanism to organize cell-cell contacts by clustering proteins. •Scaffolding proteins localize at the cytoplasmic plaque of tight junction and zonula adhaerens.•Scaffolding proteins cluster transmembrane and cytoplasmic ligands to modulate their function.•Their interaction with the actomyosin cytoskeleton is crucial for assembly and mechanoregulation.•A large fraction of scaffolding and associated proteins are predicted to undergo phase separation.