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

36 Citations (Scopus)

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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prostaglandin R2 D-isomerase
Neuregulin-1
Prostaglandin D2
Myelin Sheath
Neuroglia
Schwann Cells
G-Protein-Coupled Receptors
Proteolysis
Prostaglandins
Transcription Factors
Communication
Maintenance
Cell Membrane
Ligands
Genes
In Vitro Techniques

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Prostaglandin D2 synthase/GPR44 : A signaling axis in PNS myelination. / Trimarco, Amelia; Forese, Maria Grazia; Alfieri, Valentina; Lucente, Alessandra; Brambilla, Paola; Dina, Giorgia; Pieragostino, Damiana; Sacchetta, Paolo; Urade, Yoshihiro; Boizet-Bonhoure, Brigitte; Boneschi, Filippo Martinelli; Quattrini, Angelo; Taveggia, Carla.

In: Nature Neuroscience, Vol. 17, No. 12, 01.01.2014, p. 1682-1692.

Research output: Contribution to journalArticle

Trimarco, A, Forese, MG, Alfieri, V, Lucente, A, Brambilla, P, Dina, G, Pieragostino, D, Sacchetta, P, Urade, Y, Boizet-Bonhoure, B, Boneschi, FM, Quattrini, A & Taveggia, C 2014, 'Prostaglandin D2 synthase/GPR44: A signaling axis in PNS myelination', Nature Neuroscience, vol. 17, no. 12, pp. 1682-1692. https://doi.org/10.1038/nn.3857
Trimarco A, Forese MG, Alfieri V, Lucente A, Brambilla P, Dina G et al. Prostaglandin D2 synthase/GPR44: A signaling axis in PNS myelination. Nature Neuroscience. 2014 Jan 1;17(12):1682-1692. https://doi.org/10.1038/nn.3857
Trimarco, Amelia ; Forese, Maria Grazia ; Alfieri, Valentina ; Lucente, Alessandra ; Brambilla, Paola ; Dina, Giorgia ; Pieragostino, Damiana ; Sacchetta, Paolo ; Urade, Yoshihiro ; Boizet-Bonhoure, Brigitte ; Boneschi, Filippo Martinelli ; Quattrini, Angelo ; Taveggia, Carla. / Prostaglandin D2 synthase/GPR44 : A signaling axis in PNS myelination. In: Nature Neuroscience. 2014 ; Vol. 17, No. 12. pp. 1682-1692.
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