THE CEREBROSIDE SULFATE ACTIVATOR (SAPOSIN-B, SAP-1) - A MANY FACETED PROTEIN

The Cerebroside Sulfate Activator (CS-Act) is a small protein involved in the catabolism of cerebroside sulfates (sulfatides) and a number of other glycosphingolipids. It is also commonly referred to as SAP-1 or Saposin B. CS-Act is believed to function by binding target lipids, extracting them from membranes or micelles and making them available to water soluble enzymes. The protein probably also plays a role in intermembrane transport of these lipids. The protein is noted for exceptional thermal and proteolytic stability and a multiamphipathic helix bundle structure stabilized by internal disulfides has been proposed. CS-Act is defective in a rare form of Metachromatic Leukodystrophy and the responsible mutations have been defined. The CS-Act protein is derived from a much larger precursor. Prosaposin, which gives rise to a family of structurally similar proteins believed to have related biochemical activities. The relative abundance of CS-Act, the other Saposins and Prosaposin, as well as the anatomic and developmental profiles of these proteins and their messenger RNA suggests that they may play more profound biological roles than originally envisioned.