Fig. 5.

A step-wise recruitment of proteins to cell–cell contacts. The earliest sites of stable physical interaction during cell–cell contact formation are primordial, spot-like AJs (pAJs) or puncta at the tips of cellular protrusions. During junctional maturation, the cellular protrusions of adjacent cells interdigitate, and multiple puncta are formed along the sides of protrusions. These puncta gradually fuse to form linear arrangements of cell–cell contacts sites thus generating a zipper-like appearance. During further maturation, cell–cell contacts are formed along the entire lateral cell surface, and the zipper-like cell–cell structure disappears. Cell contact-associated proteins are recruited in a step-wise manner. The pAJs/puncta are positive for integral membrane proteins (E-cadherin, JAM-A, nectin-2), but also peripheral membrane proteins (ZO-1, α-catenin, afadin) and contain proteins associated with AJs as well as TJs in polarized cells. During the formation of zipper-like cell contacts, occludin is recruited, probably through its interaction with ZO-1. Thereafter, PAR-3 is recruited by JAM-A and/or nectin-2, and claudins are recruited, probably through interaction with ZO-1. Indirect evidence suggests that aPKC and PAR-6 appear slightly later than PAR-3. The vertical bar reflects the increase in the contacting membrane area during cell–cell contact formation