Prostaglandin D2 Synthase/GPR44: a Signaling Axis in PNS Myelination

Overview

Journal Nat Neurosci

Date 2014 Nov 3

PMID 25362470

Citations 43

Authors

Amelia Trimarco

Maria Grazia Forese

Valentina Alfieri

Alessandra Lucente

Paola Brambilla

Giorgia Dina

Damiana Pieragostino

Paolo Sacchetta

Yoshihiro Urade

Brigitte Boizet-Bonhoure

Filippo Martinelli Boneschi

Angelo Quattrini

Carla Taveggia

Affiliations

Soon will be listed here.

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.

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References

Wrabetz L, Taveggia C, Feltri M, Quattrini A, Awatramani R, Scherer S . A minimal human MBP promoter-lacZ transgene is appropriately regulated in developing brain and after optic enucleation, but not in shiverer mutant mice. J Neurobiol. 1998; 34(1):10-26. DOI: 10.1002/(sici)1097-4695(199801)34:1<10::aid-neu2>3.0.co;2-f. View

Monk K, Naylor S, Glenn T, Mercurio S, Perlin J, Dominguez C . A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science. 2009; 325(5946):1402-5. PMC: 2856697. DOI: 10.1126/science.1173474. View

Tootle T . Genetic insights into the in vivo functions of prostaglandin signaling. Int J Biochem Cell Biol. 2013; 45(8):1629-32. DOI: 10.1016/j.biocel.2013.05.008. View

Urade Y, HAYAISHI O . Prostaglandin D synthase: structure and function. Vitam Horm. 2000; 58:89-120. DOI: 10.1016/s0083-6729(00)58022-4. View

Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S . Neuregulin-1 type III determines the ensheathment fate of axons. Neuron. 2005; 47(5):681-94. PMC: 2387056. DOI: 10.1016/j.neuron.2005.08.017. View

Kao S, Wu H, Xie J, Chang C, Ranish J, Graef I . Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science. 2009; 323(5914):651-4. PMC: 2790385. DOI: 10.1126/science.1166562. View

Nagata N, Fujimori K, Okazaki I, Oda H, Eguchi N, Uehara Y . De novo synthesis, uptake and proteolytic processing of lipocalin-type prostaglandin D synthase, beta-trace, in the kidneys. FEBS J. 2009; 276(23):7146-58. DOI: 10.1111/j.1742-4658.2009.07426.x. View

Glenn T, Talbot W . Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin. Development. 2013; 140(15):3167-75. PMC: 3931731. DOI: 10.1242/dev.093401. View

Haskew-Layton R, Payappilly J, Xu H, Bennett S, Ratan R . 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) protects neurons from oxidative death via an Nrf2 astrocyte-specific mechanism independent of PPARγ. J Neurochem. 2012; 124(4):536-47. DOI: 10.1111/jnc.12107. View

10.

Beuckmann C, Lazarus M, Gerashchenko D, Mizoguchi A, Nomura S, Mohri I . Cellular localization of lipocalin-type prostaglandin D synthase (beta-trace) in the central nervous system of the adult rat. J Comp Neurol. 2000; 428(1):62-78. DOI: 10.1002/1096-9861(20001204)428:1<62::aid-cne6>3.0.co;2-e. View

11.

Bao J, Lin H, Ouyang Y, Lei D, Osman A, Kim T . Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nat Neurosci. 2004; 7(11):1250-8. DOI: 10.1038/nn1342. View

12.

Nicholson J, Puche A, Guo Y, Weinreich D, Slater B, Bernstein S . PGJ(2) provides prolonged CNS stroke protection by reducing white matter edema. PLoS One. 2013; 7(12):e50021. PMC: 3527449. DOI: 10.1371/journal.pone.0050021. View

13.

Ogata T, Iijima S, Hoshikawa S, Miura T, Yamamoto S, Oda H . Opposing extracellular signal-regulated kinase and Akt pathways control Schwann cell myelination. J Neurosci. 2004; 24(30):6724-32. PMC: 6729716. DOI: 10.1523/JNEUROSCI.5520-03.2004. View

14.

Newbern J, Li X, Shoemaker S, Zhou J, Zhong J, Wu Y . Specific functions for ERK/MAPK signaling during PNS development. Neuron. 2011; 69(1):91-105. PMC: 3060558. DOI: 10.1016/j.neuron.2010.12.003. View

15.

Hennen S, Wang H, Peters L, Merten N, Simon K, Spinrath A . Decoding signaling and function of the orphan G protein-coupled receptor GPR17 with a small-molecule agonist. Sci Signal. 2013; 6(298):ra93. PMC: 4114018. DOI: 10.1126/scisignal.2004350. View

16.

Kostenis E, Ulven T . Emerging roles of DP and CRTH2 in allergic inflammation. Trends Mol Med. 2006; 12(4):148-58. DOI: 10.1016/j.molmed.2006.02.005. View

17.

Nelson A, Loy D, Lawson J, Katseff A, FitzGerald G, Garza L . Prostaglandin D2 inhibits wound-induced hair follicle neogenesis through the receptor, Gpr44. J Invest Dermatol. 2012; 133(4):881-9. PMC: 3593761. DOI: 10.1038/jid.2012.398. View

18.

Quattrini A, Previtali S, Feltri M, Canal N, Nemni R, Wrabetz L . Beta 4 integrin and other Schwann cell markers in axonal neuropathy. Glia. 1996; 17(4):294-306. DOI: 10.1002/(SICI)1098-1136(199608)17:4<294::AID-GLIA4>3.0.CO;2-#. View

19.

Lal M, Caplan M . Regulated intramembrane proteolysis: signaling pathways and biological functions. Physiology (Bethesda). 2011; 26(1):34-44. DOI: 10.1152/physiol.00028.2010. View

20.

Irikura D, Aritake K, Nagata N, Maruyama T, Shimamoto S, Urade Y . Biochemical, functional, and pharmacological characterization of AT-56, an orally active and selective inhibitor of lipocalin-type prostaglandin D synthase. J Biol Chem. 2009; 284(12):7623-30. PMC: 2658056. DOI: 10.1074/jbc.M808593200. View