ArticleThe Journal of biological chemistry2015
The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 83 citations in OpenAlex.
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Article
- Identification of TPRA1 as a Novel Receptor and Predictive Biomarker for Oncolytic Virus M1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cilia Provide a Platform for the Generation, Regulated Secretion, and Reception of Peptidergic Signals.Cells · 2024Review
- Nuclear import of Mas-related G protein-coupled receptor member D induces pathological cardiac remodeling.Cell communication and signaling : CCS · 2023Article
- Primary cilia as dynamic and diverse signalling hubs in development and disease.Nature reviews. Genetics · 2023Review
- The ciliary lumen accommodates passive diffusion and vesicle-assisted trafficking in cytoplasm-ciliary transport.Molecular biology of the cell · 2023Article
- Compartmentalised cAMP signalling in the primary cilium.Frontiers in physiology · 2023Review
- Paralog-specific TTC30 regulation of Sonic hedgehog signaling.Frontiers in molecular biosciences · 2023Article
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- Gli Phosphorylation Code in Hedgehog Signal Transduction.Frontiers in cell and developmental biology · 2022Review
- Ciliary Type III Adenylyl Cyclase in the VMH Is Crucial for High-Fat Diet-Induced Obesity Mediated by Autophagy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Discovering of Genomic Variations Associated to Growth Traits by GWAS in Braunvieh Cattle.Genes · 2021Article
- Compartmentalized GPCR Signaling from Intracellular Membranes.The Journal of membrane biology · 2021Review
- Kinase-anchoring proteins in ciliary signal transduction.The Biochemical journal · 2021Review
- Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway.Development (Cambridge, England) · 2021Article
- Hedgehog signaling and Tre1 regulate actin dynamics through PI(4,5)PCell reports · 2021Article
- Regulation and Function of Calcium in the Cilium.Current opinion in physiology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.