title: Prostaglandin D2 synthase/GPR44: a signaling axis in PNS myelination.
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.
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Trimarco
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Forese
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Alfieri
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lucente
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brambilla
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Dina
authors.affiliation: Department of Experimental and Clinical Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Damiana
authors.initials: D
authors.lastname: Pieragostino
authors.affiliation: Department of Experimental and Clinical Sciences, University "G. D'Annunzio", Chieti, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sacchetta
authors.affiliation: International Institute for Integrative Sleep medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.affiliation: Institut de Génétique Humaine CNRS UPR1142, Montpellier, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Boizet-Bonhoure
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
authors.affiliation: 1] Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy. [2] INSPE at San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Taveggia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000648:ultrastructure; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis*; D054834:Lipocalins / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D017933:Peripheral Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D011982:Receptors, Prostaglandin / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D054834:Lipocalins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; C036293:prostaglandin D2 receptor