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 language | English |
|---|---|
| Pages (from-to) | 1682-1692 |
| Number of pages | 11 |
| Journal | Nature Neuroscience |
| Volume | 17 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Jan 1 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Prostaglandin D2 synthase/GPR44
T2 - A signaling axis in PNS myelination
AU - Trimarco, Amelia
AU - Forese, Maria Grazia
AU - Alfieri, Valentina
AU - Lucente, Alessandra
AU - Brambilla, Paola
AU - Dina, Giorgia
AU - Pieragostino, Damiana
AU - Sacchetta, Paolo
AU - Urade, Yoshihiro
AU - Boizet-Bonhoure, Brigitte
AU - Boneschi, Filippo Martinelli
AU - Quattrini, Angelo
AU - Taveggia, Carla
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84925224951&partnerID=8YFLogxK
U2 - 10.1038/nn.3857
DO - 10.1038/nn.3857
M3 - Article
C2 - 25362470
AN - SCOPUS:84925224951
VL - 17
SP - 1682
EP - 1692
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 12
ER -