NR AWOA
AU Solis,G.P.; Malaga-Trillo,E.; Schrock,Y.; Luncz,L.; Stuermer,C.A.O.
TI Conserved roles of vertebrate prion proteins II
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-34
PT Konferenz-Vortrag
AB Even though many different roles have been proposed for prion proteins (PrPs), e.g. cell adhesion, copper metabolism, neuroprotection and cell signaling, these putative functions do not converge into a molecular mechanism of physiological relevance to vertebrates. In a separate study, we show that a PrP cellular function is essential for normal development in zebrafish, and that this role might be conserved among vertebrates (see abstract by Málaga-Trillo et al.). To better understand this function, we heterologously expressed fish PrPs in mouse neuroblastoma (N2a) cells, and compared their cellular properties with those of their mouse, xenopus and chicken counterparts. Interestingly, only cells expressing the fluorescently labeled constructs show PrP accumulation at cell contacts. This suggests that a conserved role of vertebrate PrPs might be to establish homotypic transinteractions, which could be involved in cell-cell communication and signaling. To test whether this interaction between PrPs can indeed mediate the formation of cell contacts, we employed the Drosophila Schneider-2 (S2) cells, a well-established non-adhesive cell-line used to characterize cell adhesion molecules. Notably, S2 cells expressing various vertebrate PrPs acquired the ability to aggregate upon the accumulation of PrP at cell-cell contacts. Moreover, this accumulation was concomitant with the recruitment of the raft-associated reggie/flotillin proteins and the activation of tyrosine kinases, indicating that PrP-interactions between neighboring cells might elicit signal transduction events. We also showed that the repetitive, hydrophobic and globular domains, as well as the glycosylation states play differential roles in this function. Altogether, our data provide the molecular and cellular basis for this evolutionarily conserved PrP role, which may be lost or deregulated upon PrP conversion. Supported by the DFG, TR-SFB11, TSE-BW.
AD Department of Biology, University of Konstanz, 78457 Konstanz, Germany. E-mail: Gonzalo.Solis@uni-konstanz.de
SP englisch
PO Italien