Although they're famous for relaying small signaling molecules such as ions and ATP, gap junctions also display some sticky behavior: they form through the adhesion of two aligned hemichannels on adjacent cells. And yet, says Kriegstein, “an adhesive function for gap junctions has been overlooked.”
Brain cells of mice lacking a gap junction subunit called connexin43 have developmental migration delays in vivo. The defects have been assumed to be caused by faulty intercellular communications.
Kriegstein's group was also interested in migrating brain cells—in particular, radial glial cells, which give birth to neurons that migrate outwards, using the long fibers of radial glial cells as tracks. They had noticed that both fibers and neurons express gap junction proteins that might help migration. They now show that these proteins form junctions at contact points between the cells.
Loss of this connection, via knockdown of connexins, interfered with the neurons' outward migration. But a communications breakdown was not at fault: migration was restored by replacing the lost junction proteins with versions that adhered but had a closed pore. And interfering with pore communication by blocking calcium waves did not stop normal migration.
Brain cells probably don't hold the patent on gap junctions as bonding agents. “Gap junctions are nearly ubiquitous in developing cell types and adult cells as well,” says Kriegstein. “It's worth exploring whether they have adhesive roles in these systems.” Connexins found in lung tumor cells, for instance, might help them spread out.
And back in the brain, an adhesive function might explain the basis for Charcot-Marie-Tooth syndrome, which is caused by an abnormal connexin. In this disease, the myelin sheath of peripheral nerves withdraws, almost as if it is unwrapping.