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.
Prostaglandin D2 synthase/GPR44: a signaling axis in PNS myelination / A. Trimarco, M.G. Forese, V. Alfieri, A. Lucente, P. Brambilla, G. Dina, D. Pieragostino, P. Sacchetta, Y. Urade, B. Boizet Bonhoure, F.M. Boneschi, A. Quattrini, C. Taveggia. - In: NATURE NEUROSCIENCE. - ISSN 1097-6256. - 17:12(2014), pp. 1682-1692.
|Titolo:||Prostaglandin D2 synthase/GPR44: a signaling axis in PNS myelination|
|Parole Chiave:||Animals; Cells, Cultured; Female; Ganglia, Spinal; Intramolecular Oxidoreductases; Lipocalins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myelin Sheath; Nerve Fibers, Myelinated; Peripheral Nervous System; Rats; Receptors, Immunologic; Receptors, Prostaglandin; Signal Transduction; Neuroscience (all)|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/nn.3857|
|Appare nelle tipologie:||01 - Articolo su periodico|