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10.1038/nature19312 http://scihub22266oqcxt.onion/10.1038/nature19312 C5499706!5499706!27501152     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nature 2016 ; 536 (7617): 464-8 Nephropedia Template TP {{tp|p=27501152|t=2016. The prion protein is an agonistic ligand of the G protein-coupled receptor Gpr126/Adgrg6 |pdf=|usr=}}{{27501152}} gab.com Text The prion protein is an agonistic ligand of the G protein-coupled receptor Gpr126/Adgrg6 JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=27501152 #FOAvip Ablation of the cellular prion protein PrPC leads to a chronic demyelinating polyneuropathy (CDP) affecting Schwann cells. Neuron-restricted PrPC expression prevents the disease1, suggesting that it acts in trans through an unidentified Schwann cell receptor. We found that the cAMP concentration in PrPC-deficient sciatic nerves is reduced, suggesting the involvement of a G protein-coupled receptor (GPCR). The amino-terminal ?flexible tail? (FT, residues 23-120) of PrPC triggered a concentration-dependent cAMP increase in primary Schwann cells, in the Schwann-cell line SW10, and in Hek293T cells overexpressing the GPCR Gpr126/Adgrg6. In contrast, naïve HEK293T cells and HEK293T cells expressing several other GPCRs did not react to the FT, and ablation of Gpr126 from SW10 cells abolished the FT-induced cAMP response. The FT contains a polycationic cluster (KKRPKPG) similar to the GPRGKPG motif of the Gpr126 agonist, type-IV collagen2 (Col4). A KKRPKPG-containing PrPC-derived peptide (FT23-50) sufficed to induce a Gpr126-dependent cAMP response in cells and mice, and improved myelination in hypomorphic Gpr126 zebrafish mutants. Substitution of the cationic residues with alanines abolished the biological activity of both FT23-50 and the respective Col4 peptide. We conclude that PrPC promotes myelin homeostasis through FT-mediated Gpr126 agonism. Besides clarifying the physiological role of PrPC, these observations are relevant to the pathogenesis of demyelinating polyneuropathies, common debilitating diseases with limited therapeutic options. Twit Text FOAVip The prion protein is an agonistic ligand of the G protein-coupled receptor Gpr126/Adgrg6 ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=27501152 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27501152 #FOAvip English Wikipedia <ref>{{Cite pmid|27501152}}</ref> The prion protein is an agonistic ligand of the G protein-coupled receptor Gpr126/Adgrg6 #MMPMID27501152 Küffer A; Lakkaraju AK; Mogha A; Petersen SC; Airich K; Doucerain C; Marpakwar R; Bakirci P; Senatore A; Monnard A; Schiavi C; Nuvolone M; Grosshans B; Hornemann S; Bassilana F; Monk KR; Aguzzi A Nature 2016[Aug]; 536 (7617): 464-8 PMID27501152show ga Ablation of the cellular prion protein PrPC leads to a chronic demyelinating polyneuropathy (CDP) affecting Schwann cells. Neuron-restricted PrPC expression prevents the disease1, suggesting that it acts in trans through an unidentified Schwann cell receptor. We found that the cAMP concentration in PrPC-deficient sciatic nerves is reduced, suggesting the involvement of a G protein-coupled receptor (GPCR). The amino-terminal ?flexible tail? (FT, residues 23-120) of PrPC triggered a concentration-dependent cAMP increase in primary Schwann cells, in the Schwann-cell line SW10, and in Hek293T cells overexpressing the GPCR Gpr126/Adgrg6. In contrast, naïve HEK293T cells and HEK293T cells expressing several other GPCRs did not react to the FT, and ablation of Gpr126 from SW10 cells abolished the FT-induced cAMP response. The FT contains a polycationic cluster (KKRPKPG) similar to the GPRGKPG motif of the Gpr126 agonist, type-IV collagen2 (Col4). A KKRPKPG-containing PrPC-derived peptide (FT23-50) sufficed to induce a Gpr126-dependent cAMP response in cells and mice, and improved myelination in hypomorphic Gpr126 zebrafish mutants. Substitution of the cationic residues with alanines abolished the biological activity of both FT23-50 and the respective Col4 peptide. We conclude that PrPC promotes myelin homeostasis through FT-mediated Gpr126 agonism. Besides clarifying the physiological role of PrPC, these observations are relevant to the pathogenesis of demyelinating polyneuropathies, common debilitating diseases with limited therapeutic options. äThe prion protein is an agonistic ligand of the G protein-coupled rece(epmc).pdf DeepDyve Pubget Overpricing