ABSTRACT
Many proteins with a variety of functions have proven to have glycosylphosphatidylinositol (GPI)-linkages; two members of this family are the scrapie prion protein and the receptor for ciliary neurotrophic factor (CNTF). The scrapie prion protein has two isoforms: PrPC is found in brain cells from normal animals, while PrPsc is an abnormal isoform that is only found in scrapie-infected animals. PrPsc is the only identified component of the prion, an infectious agent that apparently does not contain nucleic acid. Models for how prions replicate require that PrPsc must somehow recruit PrPC and catalyze or stabilize a post-translational event that converts PrPC into PrPsc. Extensive characterization has suggested that this critical post-translational event is probably conformational and not a chemical change. The presence of a GPI anchor on CNTFRalfa is an unusual feature for a molecule that must transmit a signal to the inside of the cell. Recent data have indicated that CNTFRalfa must bind CNTF, then interact with two other "ß" receptor components to initiate signal transduction. Furthermore, we have shown that, unlike the vast majority of receptors, CNTFRalfa can function as a soluble molecule to promote CNTF action on cells that contain the two ß components, but do not themselves express CNTFRalfa. Intringuingly, we have also demostrated that CNTFRalfa is present in cerebrospinal fluid and blood in vivo, and the release of CNTFRalfa from skeletal muscle is increased by denervation of the muscle. Whether the soluble form is released through GPI-anchor cleavage remains to be determined