Passing Prion Proteins to the Cell Next Door

Science's STKE  10 Dec 2002:
Vol. 2002, Issue 162, pp. tw459-TW459
DOI: 10.1126/stke.2002.162.tw459

Liu et al. observed the transfer of glycophosphatidylinositol (GPI)-anchored proteins, including the cellular prion protein (PrPc), between cells, a process that may have implications for the pathogenesis of prion diseases. PrPc, a glycoprotein anchored to the cell membrane through GPI, has been implicated in the pathophysiology of the transmissible spongiform encephalopathies. In these neurodegenerative disorders, the prion protein assumes an abnormal configuration, PrPSc (scrapie prion protein), which is widely believed to catalyze the conversion of normal PrPc into the pathogenic form. Liu et al. cocultured M17-PrP cells, an adherent neuroblastoma cell line stably transfected with human PrPc, with IA, an anchorage-independent leukemia cell line, and demonstrated that PrPc could be transferred from one to the other after protein kinase C (PKC) activation with phorbol 12-myristate 13-acetate (PMA). PrPc transfer, detected by flow cytometry and immunostaining, was most efficient after PMA treatment of both donor and acceptor cells but could be observed after treatment of either donor or recipient alone. Transfer depended on cell-to-cell contact and required the GPI anchor: cleaving GPI with phophatidylinositol-phospholipase C reduced transfer and replacing the GPI domain with membrane and cytoplasmic domains of another protein abolished it. CD90, another GPI-anchored protein, was also transferred after treatment with PMA. PMA increased intercellular adhesion; "forcing" adhesion by centrifugation, however, did not promote transfer. PrPc was also transferred from M17-PrP cells to mouse splenocytes treated with PMA or the T cell mitogen concanavalin-A. These data suggest that PKC activation can lead to intercellular transfer of GPI-anchored proteins, a process that may have implications for the transport of the abnormal PrPSc form.

T. Liu, R. Li, T. Pan, D. Liu, R. B. Peterson, B.-S. Wong, P. Gambetti, M. S. Sy, Intercellular transfer of the cellular prion protein. J. Biol. Chem. 277, 47671-47678 (2002). [Abstract] [Full Text]