THE TAILS OF 2 PROTEINS - THE SCRAPIE PRION PROTEIN AND THE CILIARY NEUROTROPHIC FACTOR-RECEPTOR

Many proteins with a variety of functions have proven to have glycosyl phosphatidylinositol (GPI)-linkages; two members of this family are th e scrapie prion protein and the receptor for ciliary neurotrophic fact or (CNTF). The scrapie prion protein has two isoforms: PrPC is found i n brain cells from normal animals, while PrPSc is an abnormal isoform that is only found in scrapie-infected animals. PrPSc is the only iden tified component of the prion, an infectious agent that apparently doe s not contain nucleic acid. Models for how prions replicate require th at PrPSc must somehow recruit PrPC and catalyze or stabilize a post-tr anslational event that converts PrPC into PrPSc. Extensive characteriz ation has suggested that this critical post-translational event is pro bably conformational and not a chemical change. The presence of a GPI anchor on CNTFR alpha is an unusual feature for a molecule that must t ransmit a signal to the inside of the cell. Recent data have indicated that CNTFR alpha must bind CNTF, then interact with two other ''beta' ' receptor components to initiate signal transduction. Furthermore, we have shown that, unlike the vast majority of receptors, CNTFR alpha c an function as a soluble molecule to promote CNTF action on cells that contain the two beta components, but do not themselves express CNTFR alpha. Intriguingly, we have also demonstrated that CNTFR alpha is pre sent in cerebrospinal fluid and blood in vivo, and the release of CNTF R alpha from skeletal muscle is increased by denervation of the muscle . Whether the soluble form is released through GPI-anchor cleavage rem ains to be determined.