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The identification of the C3a Receptor (C3AR1) as the target of the VGF derived peptide TLQP-21 in rodent cells

Beck, Valerie and Leighton-Davies, Juliet and Beibel, Martin and Roma, Guglielmo and Oakeley, Edward James and Hamon, Jacques and Barbieri, Samuel and Preuss, Inga and Lasbennes-Eckerlen, Marie-Christine and Sailer, Andreas and Suply, Thomas and Seuwen, Klaus and Parker, Christian and Bassilana, Frederic and Lannoy, Vincent and bernard, Jerome and Hannedouche, Sebastien (2013) The identification of the C3a Receptor (C3AR1) as the target of the VGF derived peptide TLQP-21 in rodent cells. Journal of Biological Chemistry, 288 (38). pp. 27434-27443. ISSN 0021-9258

Abstract

TLQP-21, a peptide derived from VGF (non-acronymic) by proteolytic processing, has been shown to modulate energy metabolism, differentiation and cellular response to stress. Although extensively investigated, the receptor for this endogenous peptide has not previously been described.
This report describes the use of a series of studies that show G protein-coupled receptor (GPCR)-mediated biological activity of TLQP-21as well as signalling in CHO-K1 cells. Unbiased genome wide sequencing of the transcriptome of the responsive CHO-K1 cells identified a priority list of possible GPCRs bringing about this activity. Using the biological activity generated by this peptide the possible targets of this ligand were tested by screening a series of defined receptor antagonists as well as siRNAs to inhibit expression of these putative receptors.
The results of these studies are all consistent with the receptor of the TLQP-21 peptide in CHO-K1 cells being C3AR1. In addition the sensitivity of TLQP-21 signalling to pertussis toxin is also consistent with what is known about the signalling pathway of this receptor. We further demonstrate that the binding of TLQP-21 to the C3AR1 goes beyond signalling as we show thatTLQP-21 has a migratory role in RAW264.7 mouse cells

Item Type: Article
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Keywords: TLQP-21, C3AR1, RNASeq, Receptor identification, GPCR signalling, Cell migration
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Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/10262

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