Cell-Cell Adhesion Complexes as Key Conductors of Cell Behavior

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Background

Cell-cell adhesion complexes arose early in the evolution of multicellularity and have undergirded the vast diversification of metazoan life by enabling tissue organization, tissue plasticity, organ development, and body morphogenesis. Extensive research over the past few decades has demonstrated that the specific molecular complexes that form along cell-cell contacts – such as adherens junctions, tight junctions, desmosomes, and gap junctions – are essential for the establishment and maintenance of cellular architecture, cell-to-cell communication and mechanotransduction. It is also well established that perturbations in the composition and function of these cell-cell adhesion complexes can lead to a multiplicity of developmental abnormalities and diseases, such as heart disease and cancer.

Cell-cell adhesion complexes not only play structural or architectural roles; they also actively engage in signal transduction within the cell, either locally along cell-cell contacts or remotely to influence functions in other subcellular compartments. A significant body of work suggests that cell-cell adhesion complexes are key conductors of intracellular signaling pathways. Cell-cell junction components interact with growth factor receptors and kinases at the membrane; they cross-talk with metabolic regulators, small GTPases, cytoskeletal and endocytosis components, RNA-binding complexes; they shuttle to the nucleus to regulate gene expression and instruct numerous cellular functions. In reverse, cell-cell adhesion complexes are also key intermediates or endpoints of major signaling pathways that regulate cell fate and behavior. In this issue, we aim to highlight the role of cell-cell adhesion complexes as key nodes of intracellular signaling. We envision that shedding more light on the regulatory pathways that flow through cell-cell junctions will open new avenues of investigation and further define the roles of these elaborate structures in cell homeostasis and disease.

We invite submission of Original Research manuscripts and Brief Research Reports, as well as Reviews, Mini Reviews, Perspectives, Hypothesis and Theory articles, that address lingering questions or break new ground regarding the role(s) of cell-cell adhesion complexes or of their individual components in intracellular signaling and cellular behavior, either as master regulators or as key intermediates. Suggested themes - although not limited to - are as below:

• Signaling to and from tight junctions, adherens junctions, desmosomes, and gap junctions
• Interactions with signaling and growth factor pathways, kinases, phosphatases
• Emerging and novel roles of cell-cell adhesion components in the nucleus
• Roles in post-transcriptional regulation of gene expression
• Cross-talk with metabolic regulators
• Dysregulation that leads to disease through aberrant signaling, cell growth and proliferation
• Function prediction or function conservation through bioinformatic, phylogenetic, or evolutionary analyses

Keywords: Cell-cell adhesion, intracellular signaling pathways, Kinases

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