Although AJs are observed in various cell contexts (e.g., intercalated disk/fascia adherens of cardiac myocytes; paranodal loops/intracellular junctions of Schwann cells), and have historically encompassed cell-substratum adhesions (e.g., focal contacts, [2
], the most well known example is the zonular adherens junction, or zonula adherens
(ZA) of polarized epithelial cells (). The ZA was described by Farquhar and Palade as the intermediate component of a tripartite, junction complex, commonly found between the apices of most simple epithelia [3
]. The two other components of this complex, the more lumenally localized zonula occludens (or tight junction) and the basally localized desmosome are compositionally and functionally distinct and are discussed elsewhere (in this series, 2, 3, 6 & 10). At the electron microscopic level, the AJ is a region where membranes appear perfectly parallel over an intercellular space of ~200 Å and extending between 0.2–0.5µm in length [3
]. Deep-etch electron microscopy reveals that the intercellular space of the AJ is connected by numerous cylinder-like projections [4
], () and may reflect higher order structures of the transmembrane adhesive components (cadherins and nectins) discussed below. The cytoplasmic side of the adherens contact is characterized by a plate-like densification or “plaque” into which numerous microfilaments (4–7nm in diameter) feed.
Ultrastructural features of adherens junctions
At the ZA, actin microfilaments are particularly prominent and appear to be continuous with the bundle of actin filaments that encircle the cytoplasmic surface of the contact region. While the zonula adherens is continuous or “belt-like” in most epithelia, outside of the tripartite junctional complex, adherens junctions are often discontinuous, or ‘spot-like’. These latter types of adherens contacts can be seen scattered along the entire lateral surface of epithelial cells [5
] and in non-epithelial cell types such as the synaptic junctions of neurons [6
] or the tenticle-like processes between mesenchymal cells [8
]. While spot and zonular adherens junctions appear to be fundamentally similar structures, these differences likely suit different purposes. For example, spot-like junctions may favor anchoring, while a zonular “belt-like” junction enables coordination of epithelial sheet movements (described in section VI
). In epithelia, these arrangements of AJ superstructure may also reflect different stages of junctional maturation [8
As predicted from the ultrastructure, three classes of proteins are required for this AJ structure: 1) adhesion receptors spanning the intercellular space of the junction and comprising the adhesive bond (e.g., cadherin and nectin-type adhesion receptors), 2) a cytoskeletal network anchoring the adhesive components (e.g., actin), and 3) cytoskeleton/membrane “plaque” proteins that serve to link the adhesive components with the cytoskeleton (e.g., catenins and afadin). Numerous regulatory proteins can affect these core structural components, such as growth factor receptors and kinases (e.g., EGFR and src-family members) and regulators of actin dynamics (e.g., Rho and Rap family GTPases, myosin, formins. etc). Indeed, it has become clear that these regulatory components are as central to AJ structure/function as the structural components themselves, affecting assembly, trafficking, stability and higher order junctional organizations of the core adhesive components discussed below.