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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Trimarco A,Forese MG,Alfieri V,Lucente A,Brambilla P,Dina G,Pieragostino D,Sacchetta P,Urade Y,Boizet-Bonhoure B,Martinelli Boneschi F,Quattrini A,Taveggia Cdoi
10.1038/nn.3857subject
Has Abstractpub_date
2014-12-01 00:00:00pages
1682-92issue
12eissn
1097-6256issn
1546-1726pii
nn.3857journal_volume
17pub_type
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