A closer look at the cholesterol sensor

Transport of the sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP)–SREBP complex from the endoplasmic reticulum (ER) to the Golgi is the central event mediating the cholesterol-feedback process in mammalian cells. A conformational change in SCAP is a crucial step; when cholesterol levels are high, the conformation of SCAP enables the SCAP–SREBP complex to associate with an insulin-induced gene (INSIG) retention protein in the ER. By contrast, when cholesterol levels are low, SCAP switches to a conformation that enables the dissociation of the retention protein and the association of SCAP–SREBP with COP II vesicles.