OL-protocadherin ushers the migration-stimulating protein Nap1 to cell junctions (arrowheads).

Cells are usually polite and stop crawling when they run into a neighbor. But cells sometimes need to get pushy, and a membrane protein allows them to remain mobile after making contact, Nakao et al. show. The protein works by relocating a migration-promoting complex.

Cancer cells are anti-social and lose contact inhibition, the reluctance to crawl after touching other cells. However, normal cells also have to shed this restraint during wound healing and development. Nakao et al. found a possible trigger for the behavior while studying OL-protocadherin (OL-pc), a member of the cadherin family of membrane proteins that typically fasten cells together. The team found that neurons from mice missing OL-pc couldn't extend their axons. The researchers wondered whether the protein also affects cell movement.

Nakao et al. inserted the gene for OL-pc into nervous system tumor cells that normally can't make the protein. Isolated cells moseyed along, the researchers found, but they sped up in crowded cultures in which cells frequently make contact. A protein complex containing Nap1 and WAVE1 promotes migration, and Nakao et al. discovered that OL-pc delivers it to sites of cell–cell contact.

To simulate wound healing, the researchers scratched the surface of a cell culture. Cells without OL-pc slithered slowly into the scrape, maintaining contact with each other. Cells that manufactured the protein, by contrast, rushed in haphazardly, often leaving their neighbors behind. That result suggests that instead of building contacts between cells like other cadherins do, OL-pc breaks the connections that help coordinate cell behavior. Whether OL-pc contributes to cancer cells' lack of contact inhibition remains to be seen.

Nakao, S., et al.
J. Cell Biol.