A protein that shackles HIV also helps reorganize the actin cytoskeleton, as Rollason et al. show. The protein, known as tetherin, hitches actin to lipid rafts in the plasma membrane.
Tetherin made a splash last year when researchers discovered that it snares newly minted HIV particles, preventing them from exiting cells. But tetherin's unusual structure points to other functions. At the cell surface, one end of the protein embeds in a lipid raft. Tetherin then doubles back on itself and protrudes into the cell interior. Researchers have identified several proteins that fasten lipid rafts to the actin cytoskeleton, allowing the rafts to convey signals and alter cell behavior. Rollason et al. tested whether tetherin also serves as one of these links.
Using RNAi, the researchers removed the protein from intestinal epithelial cells. In many ways, the cells seemed normal. They polarized and sported the tight junctions that link them to their neighbors. But epithelial cells normally stand tall and sprout finger-like microvilli from their apical surfaces that are braced by actin filaments. In the absence of tetherin, the cells were squat. No microvilli grew, and the actin filaments bunched up at the base of the cells.
However, the researchers found that tetherin doesn't connect directly to actin. It links through intermediaries called ezrin, EBP50, and RICH2. The involvement of RICH2 might explain how tetherin supports microvilli. By switching off Rac, a GTPase that regulates actin organization, RICH2 probably helps to stabilize the actin filaments that support the microvilli.
The researchers conclude that tetherin does link lipid rafts to the actin cytoskeleton, an interaction that could help control cell shape. Tetherin might exert its impact directly on the cytoskeleton or indirectly through its effects on GTPases like Rac.