Prostaglandin D2 synthase/GPR44: A signaling axis in PNS myelination

Amelia Trimarco, Maria Grazia Forese, Valentina Alfieri, Alessandra Lucente, Paola Brambilla, Giorgia Dina, Damiana Pieragostino, Paolo Sacchetta, Yoshihiro Urade, Brigitte Boizet-Bonhoure, Filippo Martinelli Boneschi, Angelo Quattrini, Carla Taveggia

Research output: Contribution to journalArticle

Abstract

Neuregulin 1 type III is processed following regulated intramembrane proteolysis, which allows communication from the plasma membrane to the nucleus. We found that the intracellular domain of neuregulin 1 type III upregulated the prostaglandin D2 synthase (L-pgds, also known as Ptgds) gene, which, together with the G protein-coupled receptor Gpr44, forms a previously unknown pathway in PNS myelination. Neuronal L-PGDS is secreted and produces the PGD2 prostanoid, a ligand of Gpr44. We found that mice lacking L-PGDS were hypomyelinated. Consistent with this, specific inhibition of L-PGDS activity impaired in vitro myelination and caused myelin damage. Furthermore, in vivo ablation and in vitro knockdown of glial Gpr44 impaired myelination. Finally, we identified Nfatc4, a key transcription factor for myelination, as one of the downstream effectors of PGD2 activity in Schwann cells. Thus, L-PGDS and Gpr44 are previously unknown components of an axo-glial interaction that controls PNS myelination and possibly myelin maintenance.

Original languageEnglish
Pages (from-to)1682-1692
Number of pages11
JournalNature Neuroscience
Volume17
Issue number12
DOIs
Publication statusPublished - Jan 1 2014

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Trimarco, A., Forese, M. G., Alfieri, V., Lucente, A., Brambilla, P., Dina, G., Pieragostino, D., Sacchetta, P., Urade, Y., Boizet-Bonhoure, B., Boneschi, F. M., Quattrini, A., & Taveggia, C. (2014). Prostaglandin D2 synthase/GPR44: A signaling axis in PNS myelination. Nature Neuroscience, 17(12), 1682-1692. https://doi.org/10.1038/nn.3857