Cellular prion protein and GABA sub(A) receptors: No physical association?

The so-called prion diseases are probably caused by the conformational conversion of the cellular prion protein (PrP super(c)) into an abnormal, pathological form (PrP super(sc)). PrP super(c) is widely expressed in neuronal tissues, but its function is not known. From electrophysiological measurements in prion-less mice it was proposed that PrP super(c) may contribute to the structural integrity of central synapses containing gamma -aminobutyric acid type A (GABA sub(A)) receptors. We tried to substantiate this hypothesis by obtaining evidence for a structural link between the GABA sub(A) receptor and PrP super(c). Preparations of PrP super(c) and GABA sub(A) receptors, respectively, from cow brain were analysed for PrP super(c)-GABA sub(A) receptor complexes. No evidence for such complexes could be obtained in our experiments, although the protein purification schemes used should favour the preservation of intermolecular linkages. We conclude that further data concerning interactions of PrP super(c) with other proteins are needed to obtain insight into its normal functional role.