STALLing for signaling

Extracellular receptors anchored in the plasma membrane outer leaflet somehow entice intracellular proteins to the cytosolic side of the membrane for activation. Companion studies by Suzuki et al. (pages 717 and 731) give a peek at these dynamics at the level of single molecules.

The team shows that liganded clusters of the GPI-anchored receptor (GPI-AR) CD59 undergo temporary immobilizations, called STALLs (stimulation-induced temporary arrest of lateral diffusion), which serve as fleeting platforms for activating a signaling cascade. How a signal gets from the outside in without a transmembrane stretch has been intensely investigated.

When GPI-ARs come together, a slew of events take place inside the cell: the cluster can associate with Gα proteins, activate Src-family kinases (such as Lyn), and trigger the IP3/calcium signaling cascade. Previous studies based on large aggregates...