The journey of a cluster of GPI-anchored proteins around the cell membrane includes occasional stops (arrows).

At first glance, some of the cell's communication proteins seem ill-suited for the job. They are embedded in the outer layer of the plasma membrane and have no direct connection to the cell interior. Yet they manage to relay signals across the membrane. The proteins tend to congregate, and on page 169, Chen et al. show that this gregariousness might enable them to link to the cytoskeleton, a step necessary to pass on messages.

The study focused on GPI-anchored proteins (GPIAPs), some of which interconnect and spur cell division. Cross-linked GPIAPs band together with lipids and other molecules to form clusters that travel together around the membrane. Scientists suspect that these structures permit communication, but they do not understand the mechanism.

By treating fibroblasts with gold particles coated in antibodies, Chen et al. forced two kinds of GPIAPs to clump. These clusters halted for up to 10 seconds, a behavior dependent on cholesterol and Src kinases.

The authors hypothesize that, during the stops, proteins in the patches connect to the underlying cytoskeleton. Supporting that conclusion, the cystic fibrosis transmembrane conductance regulator, which does span the membrane, also shows the intermittent stops. But a version that cannot bind to the cytoskeleton just keeps drifting. The researchers propose that clusters unite GPIAPs with a membrane-bridging molecule that links to the cytoskeleton. The identity of this connector remains elusive, however.