Related Experiment Video
Updated: Jun 19, 2026
16:16
Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
Published on: September 13, 2013
Proton-sensing G-protein-coupled receptors
Marie-Gabrielle Ludwig1, Miroslava Vanek, Danilo Guerini
1Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
Nature
|September 5, 2003
Summary
New research identifies ovarian cancer G-protein-coupled receptor 1 (OGR1) as a proton-sensing receptor crucial for pH homeostasis. This discovery sheds light on the molecular mechanisms regulating blood pH levels.
Area of Science:
- Physiology
- Molecular Biology
- Biochemistry
Background:
- Blood pH is tightly regulated around 7.4 through respiration and renal mechanisms.
- The precise molecular pathways governing pH homeostasis remain incompletely understood.
- The skeleton acts as a buffer, and osteoblasts respond to pH shifts, but their sensing mechanism is unknown.
Purpose of the Study:
- To identify novel molecular players involved in pH homeostasis.
- To investigate the role of ovarian cancer G-protein-coupled receptor 1 (OGR1) in pH sensing.
- To explore the function of GPR4 and OGR1 in bone cells.
Main Methods:
- Site-directed mutagenesis to identify key amino acids in pH sensing.
- Assays for inositol phosphate and cyclic AMP formation in response to pH changes.
- Immunohistochemistry to detect OGR1 expression in rat tissues.
Main Results:
- OGR1 functions as a proton-sensing receptor, activating inositol phosphate formation between pH 6.8 and 7.8.
- Histidine residues on the extracellular surface of OGR1 are critical for pH sensing.
- GPR4, a related receptor, also senses pH but modulates cyclic AMP levels.
- OGR1 is expressed in osteosarcoma cells, osteoblast precursors, osteoblasts, and osteocytes, mediating pH-dependent signaling.
Conclusions:
- OGR1 and GPR4 are identified as key proton-sensing receptors.
- These receptors play a significant role in maintaining physiological pH homeostasis.
- OGR1 is implicated in pH sensing within the skeletal system, particularly in osteoblasts and osteocytes.
Related Concept Videos
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
01:15G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
01:21G-Protein Gated Ion Channels
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Sensory organs,...
01:15G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
01:30Transducer Mechanism: G Protein–Coupled Receptors
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
GPCRs are also called heptahelical, 7TM, or...