Cell-to-cell communication: current views and future perspectives

Abstract

Multicellular organisms rely on complex and tightly regulated communication between individual cells embedded in a dense extracellular matrix. Through the course of evolution, diverse mechanisms underlying this communication have appeared. These include communication via direct cell–to-cell contact (e.g., Delta/Notch signalling), the release of soluble factors (e.g., hormones, cytokines) that activate target cells locally or distantly through surface receptors and the direct transfer of signals through gap junction channels that span the plasma membranes of adjacent cells. During the last decade in particular, exciting progress has been made in the understanding of intercellular communication and new signalling pathways between mammalian cells have been discovered: exosomes, which are small vesicles released by cells that can be taken up by other cells; cytonemes, which are long thin membrane protrusions of cells implicated in the long-distance signalling of morphogens; tunnelling nanotubes, which are recognized as thin membranous bridges connecting distant cells that facilitate the intercellular transfer of various cellular cargo; and bioelectrical signalling in which slow changes in the resting potential of cells provide signalling cues for the regulation of cell proliferation, migration and differentiation. A second advance in our understanding of cell-to-cell communication has resulted from the development of new technologies. These are primarily imaging methods suitable for recording cells in living organisms (e.g., 2-photon microscopy) but also include micromanipulation tools (e.g., laser nanosurgery) that permit the perturbation of cells or substructures therefrom, in a natural tissue environment. This Special Issue represents a sample of various areas related to cell-to-cell interactions and in which significant advances have led to new concepts of cell–cell communication. The first part focuses on selected mechanisms of signalling pathways between cells and the second part highlights the power of advanced technology that has provided a breakthrough or shows great potential for applications regarding the analysis of cell-to-cell communication in vivo. In the following, we will briefly introduce the review articles published in this Special Issue.