Mechanosignaling

What is the role of plaque proteins in adherens junction assembly?

Cytoplasmic plaque of adherens junctions

One of the primary roles of cell-cell adhesion complexes is to connect the actomyosin network of one cell to that of neighboring cells and facilitate the generation and transduction of mechanical forces at their interface [1][2][3]

All cell-cell adhesion complexes are composed of intercellular and cytoplasmic components. Intercellular interactions are generally facilitated by cell-adhesion molecules (CAMs) such as cadherin or nectin, often in a calcium-dependent process. The complexity of the cytoplasmic region on the other hand has yet to be fully defined. This region, which has been visualized as a dense plaque of proteins (reviewed in [4]) that contains a vast array of structural and scaffolding proteins as well as regulatory proteins. These regulatory proteins mediate adhesion dynamics, including assembly and disassembly and will be discussed in greater detail in Regulation of Adhesion Dynamics.

In its most simplistic arrangement, the cytoplasmic component of AJs can be described as containing several core components. These include p120-catenin, which is bound to cadherin at the juxtamembrane position [5] and β-catenin or plakoglobin, which are bound to the cytoplasmic tail [6]. α-catenin, which also binds to β-catenin, then links the complex to the actin cytoskeletal network. Although these proteins form the core components of AJs, and have been shown to be indispensable for adhesion function, a substantial body of research indicates a far greater complexity.

Interactions between cadherin and β-catenin, which occur shortly after the proteins are translated and before cadherin integrates into the membrane [7][8], facilitate further interactions with other adaptor proteins. These interactions may influence the activity of regulatory proteins such as GAPs and GEFs, tyrosine and serine/threonine kinases and phosphatases however they also facilitate the assembly of a physical link that is capable of mechano-signalling and force transduction. The structural composition of the plaque region is discussed below. It should be noted despite significant advancements in the field in recent years, the specifics of AJ composition and recruitment have yet to be fully defined.

Adherens junctions vs Desmosomes

Different types of adhesion complexes exist, each with their own composition. For example, while the classical cadherins in adherens junctions (AJs) are bound to catenins such as β-catenin and p120 catenin which subsequently bind to the F-actin cytoskeletal network, desmosomal cadherins, bind to distinct cytoplasmic proteins such as plakoglobin (also known as γ-catenin) which in turn link to intermediate filaments. This variation exists despite desmosmal cadherins possessing a similar domain organization to the classical cadherins [9]. In this case the adhesion complex, known as a desmosome, is found in tissues subjected to higher levels of mechanical stress [10].

References

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6. Ozawa M, Ringwald M, and Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc. Natl. Acad. Sci. U.S.A. 1990; 87(11):4246-50. [PMID: 2349235]
7. Chen YT, Stewart DB, and Nelson WJ. Coupling assembly of the E-cadherin/beta-catenin complex to efficient endoplasmic reticulum exit and basal-lateral membrane targeting of E-cadherin in polarized MDCK cells. J. Cell Biol. 1999; 144(4):687-99. [PMID: 10037790]
8. Hinck L, Näthke IS, Papkoff J, and Nelson WJ. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J. Cell Biol. 1994; 125(6):1327-40. [PMID: 8207061]
9. Thomason HA, Scothern A, McHarg S, and Garrod DR. Desmosomes: adhesive strength and signalling in health and disease. Biochem. J. 2010; 429(3):419-33. [PMID: 20626351]
10. Brasch J, Harrison OJ, Honig B, and Shapiro L. Thinking outside the cell: how cadherins drive adhesion. Trends Cell Biol. 2012; 22(6):299-310. [PMID: 22555008]