Introduction of ADGRF1

ADGRF1, also known as G protein-coupled receptor 110 (GPR110) or G protein-coupled receptor PGR19, is a protein encoded by the human GPR110 gene. As a member of the G-protein coupled receptor 2 family, it is characterized by an extended extracellular region with a variable number of N-terminal protein modules coupled to a TM7 region via a domain known as the GPCR-Autoproteolysis Inducing (GAIN) domain.

Function of ADGRF1 Membrane Protein

ADGRF1 is an orphan receptor that belongs to the adhesion GPCR family and has seven transmembrane (7TM) helices with multiple N-linked glycosylation sites. The molecular mass of ADGRF1 is about 100 kD, but lower molecular weight isoforms, as well as differentially glycosylated forms, have also been reported. Studies have shown that the expression of ADGRF1 is very low in mammalian tissues except for kidney. However, a recent study showed that expression of ADGRF1 is critical in neuron development, ADGRF1 knockout mice show significant deficits in object recognition and spatial memory of mice. What’s more, ADGRF1 is thought to be a proto-oncogene based on its high expression in lung cancer, prostate cancer, high-risk acute lymphocytic lymphoma, and glioma. And synaptamide-activated ADGRF1 signaling is an important molecular mechanism for the neurodevelopmental actions of omega-3 fatty acids as ADGRF1 has the ability to mediate synaptamide-induced neurite growth and synaptogenesis in cortical neurons and neurogenic differentiation of NSCs.

Fig.1 Molecular and cellular signaling mechanisms for the neurodevelopmental and neurotrophic effects of synaptamide. (Kim, et.al. 2018)

Application of ADGRF1 Membrane Protein in Literature

1. Shi H., Zhang S. Expression and prognostic role of orphan receptor GPR110 in glioma. Biochemical and biophysical research communications. 2017, 491(2): 349-54. PubMed ID: 28728843

This article reveals that GPR110 is highly expressed in patients with glioma, which is correlated with advanced disease stages. And it can be used as an independent prognostic biomarker for the overall survival of glioma patients.

2. Bhat RR., et.al. GPCRs profiling and identification of GPR110 as a potential new target in HER2+ breast cancer. Breast cancer research and treatment. 2018, 170(2): 279-292. PubMed ID: 29574636

This article indicates that GPR110 plays a potential role in tumorigenicity and in tumor cell dissemination in HER2+ BC.

3. Ma B, et.al. Gpr110 deficiency decelerates carcinogen-induced hepatocarcinogenesis via activation of the IL-6/STAT3 pathway. American journal of cancer research. 2017, 7(3): 433. PubMed ID: 28401002

This article proves that the absence of Gpr110 decelerates liver fibrosis/cirrhosis progressing into tumorigenesis, which indicates that targeting Gpr110 and activating the IL-6/STAT3 pathway may be considered to be preventive methods for some cirrhosis transition.

4. Lee JW., et.al. Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function. Nature communications. 2016, 7: 13123. PubMed ID: 27759003

This article suggests that GPR110 can be used as a functional synaptamide receptor which provides a novel target for neurodevelopmental control and new insight into mechanisms by which DHA promotes brain development and function.

5. Lum AM., et.al. Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer. BMC cancer. 2010, 10(1): 40. PubMed ID: 20149256

This report indicates that GPR110 may play a role in tumor physiology and it can be used as a potential therapeutic candidate and disease marker for both lung and prostate cancer.

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Reference

1. Kim,et.al. (2018). N-Docosahexaenoylethanolamine: A neurotrophic and neuroprotective metabolite of docosahexaenoic acid. Molecular aspects of medicine. S0098-2997(18), 30024-4.

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