Interplay between tight junctions & adherens junctions

Abstract

Cell-cell adhesions are critical for the development and maintenance of tissues. Present at sites of cell-cell contact are the adherens junctions and tight junctions. The adherens junctions mediate cell-cell adhesion via the actions of nectins and cadherins. The tight junctions regulate passage of ions and small molecules between cells and establish cell polarity. Historically, the adherens and tight junctions have been thought of as discrete complexes. However, it is now clear that a high level of interdependency exists between the two junctional complexes. The adherens junctions and tight junctions are physically linked, by the zonula occludens proteins, and linked via signaling molecules including several polarity complexes and actin cytoskeletal modifiers. This review will first describe the individual components of both the adherens and tight junctions and then discuss the coupling of the two complexes with an emphasis on the signaling links and physical interactions between the two junctional complexes.

Fig. 1. Schematic of the adherens junctions and tight junctions

The adherens junctions are composed of the nectin-based adhesions and the cadherin-based adhesions. The extracellular domains of nectins dimerize with nectins on neighboring cells and the cyotplasmic tail recruits afadin. Similarly, cadherins bind to cadherins on adjacent cells. The cadherin cytoplasmic tail recruits β-catenin which in turn binds α-catenin. More apical to the adherens junctions are the tight junctions. The main constituents of the tight junctions are two transmembrane spanning proteins (occludin and claudin). Occludin recruits ZO-1, an actin binding protein, that can during the formation of cell-cell junctions bind to the adherens junction protein, α-catenin. The brown lines indicate the plasma membranes of two adjacent cells.

Fig. 2. Model for the coupling of tight junction assembly to adherens junctions

A) During the formation of cell-cell contact, the membranes of adjacent cells protrude toward one another. Nectins on one cell bind nectins on neighboring cells and recruit afadin which in turn binds ZO-1. The nectins form a transient adhesion that brings two opposing membranes into close proximity. (B) The extracellular domains of cadherins dimerize with cadherins on adjacent cells and the cytoplasmic domain recruits β-catenin recruits α-catenin, an afadin binding protein. C) As the adherens junctions continue to mature, ZO-1 interacts transiently with α-catenin. D) The tight junctions begin to form, ZO-1 binds occludin, and then tight junctions migrate more apically. The brown lines indicate the plasma membranes of two adjacent.