Parkinson's disease-associated receptor GPR37 is an ER chaperone for LRP6.
Wnt/β-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky β-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/β-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis. We conclude that GPR37 is crucial for cellular protein quality control during Wnt signaling.
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Birgit S
BS
Berger
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany s.perezacebron@DKFZ-Heidelberg.de niehrs@DKFZ-Heidelberg.de.
Sergio P
SP
Acebron
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Jessica
J
Herbst
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Stefan
S
Koch
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany s.perezacebron@DKFZ-Heidelberg.de niehrs@DKFZ-Heidelberg.de.|Institute of Molecular Biology, Mainz, Germany.
Christof
0000-0002-9561-9302
C
Niehrs
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D010766:Phosphorylation; D059748:Proteolysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
C509804:Gpr37 protein, mouse; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D018832:Molecular Chaperones; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins
ER‐associated degradation; GPR37; LRP6; PAEL‐R; Wnt signaling