Evidence for an association of prion protein and sphingolipid-mediated signaling.

Abstract:

:The physiological function of the cellular prion protein (PrP(c)) is unclear. PrP(c) associates with lipid rafts, highly glycolipid-rich membrane domains containing a large variety of signaling molecules, e.g., sphingolipids (SL). In this study, we investigated possible connections between PrP(c) and sphingolipid-associated signaling pathways. Using PrP(c)-wt and PrP(c)-k.o. hippocampal cell lines and mouse brains we showed higher activity of neutral and acid sphingomyelinase (SMase) in PrP(c)-k.o.-groups, while ceramide and sphingomyelin-levels were unchanged. Furthermore, despite lower basal expression levels of sphingosine kinase (SphK) in PrP(c)-k.o.-groups, the levels of its metabolite sphingosine-1-phosphate were increased, whereas S1P(3)-receptor expression was higher in PrP(c)-wt-groups again. In addition, we detected enhanced activity of phospholipase D1, an enzyme that seems to be suitable to act as a connector between the S1P(3) receptor and continuative signaling. Finally, evidence for an impact on downstream signaling cascades, especially activation of the PI3K/Akt pathway, was found. In summary, our data suggest that PrP(c) is involved in sphingolipid-associated signaling, modulating pathways that exert anti-apoptotic functions, hence indicating that PrP(c) plays a role in neuroprotection.

journal_name

J Neurochem

authors

Schmalzbauer R,Eigenbrod S,Winoto-Morbach S,Xiang W,Schütze S,Bertsch U,Kretzschmar HA

doi

10.1111/j.1471-4159.2008.05498.x

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

1459-70

issue

3

eissn

0022-3042

issn

1471-4159

pii

JNC5498

journal_volume

106

pub_type

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