A vesicle of aquaporin-3 (arrow) heads (top to bottom) for the initial contact site between two cells.

When one epithelial cell meets another, it immediately begins to polarize its membrane, as Nejsum and Nelson report on page 323. The researchers describe the mechanism that helps create distinct membrane domains by delivering characteristic proteins.

As an epithelial cell polarizes, the basolateral portion of the cell membrane—the sides and bottom—accumulates one set of proteins, whereas another set takes up residence in the apical, or upper, surface. Researchers know more about how cells keep these two regions unique than about how the difference arises. Studies suggest that, as fresh proteins emerge from the Golgi apparatus, they carry an address that directs them toward a specialized patch on the membrane. Nejsum and Nelson wanted to determine how and when this patch assembles and when cell polarity appears.

The researchers followed the travels of two membrane proteins as they left the Golgi apparatus: the basolateral aquaporin-3 and the apical aquaporin-5. Nejsum and Nelson found that vesicles packed with aquaporin-3 homed in on sites where cells had just made contact. The protein congregated with E-cadherin, which builds up at these intersections and helps lash neighboring cells together. Aquaporin-5, by contrast, spread around the cell membrane.

Previous work suggested that, in polarized cells, three components spirit proteins from the Golgi apparatus to the membrane. Vesicles ride microtubules to the edge of the cell. There, a protein complex called Exocyst ties the containers to the membrane until the SNARE complex can help plug in the proteins. Nejsum and Nelson wanted to find out when this mechanism was set up and started working. Aquaporin-3 showed a haphazard distribution if the scientists disrupted either complex, or if they broke up microtubules. The findings indicate that, immediately after cells touch, Exocyst, the SNARE complex, and microtubules team up to guide basolateral proteins to the contacting membrane, thus establishing cell polarity. The next question is how Exocyst and SNARE get into position at the sites of cell contact.