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Internalization of PrP 106–126 by the formyl‐peptide‐receptor‐like‐1 in glial cells
Author(s) -
Brandenburg LarsOve,
Koch Thomas,
Sievers Jobst,
Lucius Ralph
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04351.x
Subject(s) - internalization , endocytosis , microbiology and biotechnology , receptor , microglia , formyl peptide receptor , biology , phospholipase d , signal transduction , chemotaxis , biochemistry , immunology , inflammation
Recent studies suggest that the formyl‐peptide‐receptor‐like‐1 (FPRL1) plays an essential role in inflammatory responses in the host defence mechanisms and neurodegenerative disorders. Furthermore, it may be involved in proinflammatory processes of prion diseases. However, little is known about the induction and regulation of PrP 106–126 ‐induced receptor endocytosis. We have thus analysed whether PrP 106–126 increases the activity of phospholipase D (PLD) via FPRL1, an enzyme involved in the regulation of the secretion, endocytosis and receptor signalling, in glial cells. PLD activity was determined using a transphosphatidylation assay and the internalization of PrP 106–126 , and FPRL1 was assessed by fluorescence microscopy and quantified by ELISA. We could show that PLD is activated by PrP 106–126 both in astrocytes and microglia, and moreover that PrP 106–126 is rapidly internalized via FPRL1 in astrocytes and microglia cells. The determination of receptor activity by extracellular signal‐regulated kinases 1/2 phosphorylation and cAMP level measurement verified the PrP 106–126 ‐induced activation of FPRL1. FPRL1‐mediated PrP 106–126 uptake was blocked by the receptor antagonist chenodeoxycholic acid. These studies indicate the involvement of FPRL1‐mediated cellular signalling in PrP 106–126 ‐endocytosis and may allow the development of therapeutic agents interfering with prion uptake and/or PLD function, using either PLD or the FPRL1 as a possible pharmaceutical target.