897) during the shortening of the manuscript but would like to add it back to the manuscript: Direct coupling of PrPC to mGluR5 has been reported for an unrelated ligand, the laminin gamma-1 chain (Beraldo et al., 2010). Beraldo, F.H., Arantes, C.P., Santos, T.G., Machado, C.F., Roffe, M., Hajj, G.N., Lee, K.S., Magalhaes, A.C., Caetano, F.A., Mancini, G.L., Lopes, M.H., Americo, T.A., Magdesian, M.H., Ferguson, S.S., Linden, R., Prado, M.A., and Martins, V.R. (2011). Metabotropic glutamate receptors transduce signals for neurite outgrowth after binding of the prion

protein to laminin gamma1 chain. FASEB J. 25, 265–279. The manuscript MAPK Inhibitor Library order has been corrected online. “
“Important publications describing the effects of cytokines in the nervous system are demanding increasing amounts of our attention these days. Consider, for example, the chemotactic cytokines or chemokines. These small proteins have been extensively studied because of their importance in regulating leukocyte migration and inflammation. Approximately 50 different chemokines

have been shown to exist in higher vertebrates. These can be organized into four subfamilies based on structural considerations and, as far as we know, all their effects are transduced by a family of G protein coupled receptors (GPCRs). In most instances, chemokines are not expressed at high concentrations, their expression being upregulated in association with an innate immune or inflammatory response. Bleomycin in vivo However, one chemokine does not fit this general description. Stromal cell-derived factor-1 (SDF-1, also called CXCL12) and its receptor CXCR4 Rebamipide are constitutively expressed at high levels in many tissues, including the nervous system (Li and Ransohoff 2008). Evolutionary considerations have indicated that CXCL12 is the most ancient chemokine and that it existed in animals prior to the development of a sophisticated immune system, suggesting that the original function of chemokine signaling had nothing to do with immunity (Huising et al., 2003). The ancient function of CXCL12/CXCR4

signaling appears to involve regulating the migration and development of the stem cells that generate nearly every tissue (Miller et al., 2008). Both CXCL12 and CXCR4 are highly expressed in the developing embryo, their distribution changing rapidly over time in association with the development of different structures. The overall importance of CXCR4 signaling during development has become abundantly clear from examination of CXCR4 knockout mice, which exhibit numerous phenotypes relating to the formation of nearly every tissue (Li and Ransohoff 2008). CXCR4 signaling regulates the development of many structures in the brain and peripheral nervous system, including parts of the cerebellum, cortex, and hippocampus and the dorsal root and sympathetic ganglia.