Sphingosine kinase-dependent migration of immature dendritic cells in response to neurotoxic prion protein fragment.

The concept that circulating dendritic cells mediate neuroinvasion in transmissible spongiform encephalopathies received strong support from recent observations that prion protein is expressed in myeloid dendritic cells. We observed that prion protein fragment 106-126 is a chemoattractant for monocyte-derived immature but not mature dendritic cells. Signaling events in chemotaxis involved enzymes downstream of G(q) protein and were inhibited by blockade of sphingosine kinase, suggesting transactivation of sphingosine-1-phosphate-dependent cell motility by prion protein.