Internalization of transferrin (green)-bound receptor is blocked in cells lacking plasma membrane PIP2 (red cells).

Phosphoinositides (PIs) get the boot on page 377. Using a new method to eliminate PI(4,5)P2 from the plasma membrane, Varnai et al. create problems for receptor endocytosis and ion channels.

Until now, changing cellular PI levels in vivo meant playing the waiting game: express a kinase or phosphatase to make or eliminate a lipid species, and then wait half a day for the change to take place. During this lag, the gradual, persistent lipid modifications initiate trafficking and signaling events that distort the more immediate effect on any particular function.

Varnai and colleagues have now devised a quicker way to drop lipid levels. They hooked a drug-inducible plasma membrane targeting domain to a phosphatase that hydrolyzes PIP2. Add the drug, and voila: comparatively instant gratification...

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