| First Author | Trimarco A | Year | 2014 |
| Journal | Nat Neurosci | Volume | 17 |
| Issue | 12 | Pages | 1682-92 |
| PubMed ID | 25362470 | Mgi Jnum | J:219412 |
| Mgi Id | MGI:5620808 | Doi | 10.1038/nn.3857 |
| Citation | Trimarco A, et al. (2014) Prostaglandin D2 synthase/GPR44: a signaling axis in PNS myelination. Nat Neurosci 17(12):1682-92 |
| abstractText | 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. |
