Fig. 4

Cellular mechanisms for sensing and responding to altered cholesterol levels. Left: Low cholesterol levels lead to upregulation of cholesterol synthesis and uptake. SCAP senses low cholesterol levels and takes SREBP2 from Golgi to the endoplasmic reticulum (ER) for activation, after which SREBP2 enters nucleus and activates target gene transcription. Right: High cholesterol levels lead to increased cholesterol efflux and decreased cholesterol uptake and synthesis. Here also SCAP acts as a cholesterol sensor. Cholesterol binds to SCAP causing it to retain the SREBP2 in the ER to prevent its transport to the nucleus. INSIG proteins play a central role in this process by regulating the SREBP2-SCAP complex assembly