RGD Reference Report - Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the internalization and signal transduction of amyloid beta 1-42 in glial cells. - Rat Genome Database

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Involvement of formyl-peptide-receptor-like-1 and phospholipase D in the internalization and signal transduction of amyloid beta 1-42 in glial cells.

Authors: Brandenburg, L-O  Konrad, M  Wruck, C  Koch, T  Pufe, T  Lucius, R 
Citation: Brandenburg LO, etal., Neuroscience. 2008 Oct 2;156(2):266-76. doi: 10.1016/j.neuroscience.2008.07.042. Epub 2008 Aug 5.
RGD ID: 12910993
Pubmed: PMID:18723082   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2008.07.042   (Journal Full-text)

Recent studies suggest that the formyl-peptide-receptor-like-1 (FPRL1) plays an essential role in the inflammatory responses of host defense mechanisms and neurodegenerative disorders such as Alzheimer's disease (AD). We therefore analyzed whether amyloid beta1-42 (Abeta1-42) increased the activity of phospholipase D (PLD) via FPRL1, which is an enzyme involved in the secretion, endocytosis and receptor signaling. PLD activity was determined using a transphosphatidylation assay. The internalization of Abeta1-42 via FPRL1 was visualized using fluorescence microscopy and quantified by ELISA (Enzyme Linked Immunosorbent Assay). Determining receptor activity by extracellular-signal regulated kinases 1/2 (ERK1/2) phosphorylation and cAMP level measurement verified the Abeta1-42-induced activation of FPRL1. We were able to show that Abeta1-42 is rapidly internalized via FPRL1 in astrocytes and microglia. PLD was additionally activated by Abeta1-42 and via FPRL1 in rat glial cells. Furthermore, the ERK1/2 phosphorylation by FPRL1 agonists was dependent on the PLD product phosphatidic acid (PA). Together, these data suggest that PLD plays an important role in the regulation of Abeta1-42-induced endocytosis and FPRL1 receptor signaling.

Objects referenced in this article
Gene Fpr2 formyl peptide receptor 2 Rattus norvegicus

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