Ca2+ of cell 1 of cell 2 membrane membrane < 0.05 mM Ca2+ (B) plasma membrane of cell 1 plasma membrane of cell 2 Figure 19–6 Cadherin structure and function. (a) the extracellular region of a classical cadherin contains five copies of the extracellular cadherin domain (see Figure 19–4) separated by flexible hinge regions. Ca2+ ions (red dots) bind in the neighborhood of each hinge, preventing it from flexing. as a result, the extracellular region forms a rigid, curved structure as shown here. to generate cell–cell adhesion, the cadherin domain at the N-terminal tip of one cadherin molecule binds the N-terminal domain from a cadherin molecule on another cell. the structure was determined by x-ray diffraction of the crystallized C-cadherin extracellular region. (B) In the absence of Ca2+, increased flexibility in the hinge regions results in a floppier molecule that is no longer oriented correctly to interact with a cadherin on another cell—and adhesion fails. (C) at a typical cell–cell junction, an organized array of cadherin molecules functions like Velcro to hold cells together. Cadherins on the same cell are thought to be coupled by side-to-side interactions between their N-terminal head regions, resulting in a linear array like the alternating green and light green cadherins on the lower cell shown here. these arrays are thought to interact with similar linear arrays on an adjacent cell (blue cadherin molecules, top cell). the linear arrays on one cell are perpendicular to those on the other cell, as indicated by the red arrows. Multiple perpendicular arrays on both cells interact to form a tight-knit mat of cadherin proteins. (a, based on t.J. Boggon et al., Science 296:1308–1313, 2002; C, based on O.J. harrison et al. Structure 19:244–256, 2011.)
Cadherin-Dependent Cell–Cell adhesion Guides the Organization of Developing tissues
Cadherins form specific homophilic attachments, explaining why there are so many different family members. Cadherins are not like glue, making cell surfaces generally sticky. Rather, they mediate highly selective recognition, enabling cells of a similar type to stick together and to stay segregated from other types of cells.
Selectivity in the way that animal cells consort with one another was first demonstrated in the 1950s, long before the discovery of cadherins, in experiments in which amphibian embryos were dissociated into single cells. These cells were then mixed up and allowed to reassociate. Remarkably, the dissociated cells often reassembled into structures resembling those of the original embryo (Figure 19–7). These experiments, together with numerous more recent experiments, reveal that selective cell–cell recognition systems make cells of the same differentiated tissue preferentially adhere to one another.
Figure 19–7 Sorting out. Cells from different layers of an early amphibian embryo will sort out according to their origins. In the classical experiment shown here, mesoderm cells (green), neural plate cells (blue), and epidermal cells (red) have been disaggregated and then reaggregated in a random mixture. they sort out into an arrangement reminiscent of a normal embryo, with a “neural tube” internally, epidermis externally, and mesoderm in between. (Modified from p.L. townes and
J. holtfreter, J. Exp. Zool. 128:53–120, 1955. With permission from Wiley-Liss.)