Emond et al. reveal a new mechanism that enables cells to stick to each other.
Cadherins make cells clingy, allowing them to adhere to their neighbors. This attachment occurs when cadherins on one cell interlock with matching molecules on an adjacent cell. However, the importance of one class of cadherins, the protocadherins, for cell–cell binding is unclear. The molecules are only slightly sticky, and some studies have dismissed their role in intercellular adhesion. The researchers previously discovered that one of these proteins, Protocadherin-19 (Pcdh19), teams up with the “classical” adhesion protein N-cadherin to guide cell movements during zebrafish development.
Emond et al. now suggest that the two molecules form a fastener that helps latch cells together. Beads carrying the extracellular sections of either Pcdh19 or a nonadhesive mutant of N-cadherin weren't sticky, but beads glommed onto each other if they carried segments of both molecules. The researchers obtained similar results when they transfected a cell line that doesn't normally make either protein with Pcdh19, nonadhesive N-cadherin, or both. Cells that carried only Pcdh19 clung weakly, whereas cells sporting the mutant N-cadherin remained unattached. But cells expressing both proteins formed clumps.
Further experiments on mutant versions of both proteins suggested that Pcdh19 is the main adhesion molecule, whereas N-cadherin augments Pcdh19’s stickiness, possibly by distorting the molecule to expose the adhesion site.