ADGRB1 and Associated Diseases
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Overview of ADGRB1
Adhesion G protein-coupled receptor B1 (ADGRB1; formerly BAI1, brain-specific angiogenesis inhibitor 1) was initially identified as a target for the p53 tumor suppressor in glioblastoma cells. However, its expression was regulated through epigenetic regulation independently of p53 expression. ADGRB1 is widely expressed in both fetal and adult brains. The ADGRB1 mRNA level is high in the cerebral cortex, hippocampus, olfactory bulb, thalamic nuclei, and basal ganglia. The fact that ADGRB1 is expressed in multiple cell types of various tissues suggests that ADGRB1 has distinct functions, depending on various cellular environments.
Adhesion ADGRB1 in Disease
ADGRB1 protein plays a variety of roles in anti-angiogenesis, neuronal function, synaptogenesis, immune response, tumorigenesis, and phagocytosis.
- Neuropsychiatric Disorders
The latrophilins/ADGRL1-3 and BAIs/ADGRB1-3 appear to be critical for synapse formation and strengthening. ADGRB1 and B3 are critical for dendritic maturation and stability. Knockdown of B1 in cultured neurons results in drastically altered dendritic spine morphology, and genetic deletion of B1 induces perturbations to the postsynaptic density (PSD) regions of excitatory synapses in vivo as well as impairments in synaptic plasticity and spatial memory. Increasing evidence suggests that ADGRB1 plays an important role in the pathogenesis of psychiatric and neurological disorders such as Parkinson's disease.
- Cancer
Angiogenesis is critical for tumor growth. Several adhesion G protein-coupled receptors (aGPCRs) may regulate angiogenesis in multiple ways. Among these, ADGRB1 may be the most important as it is known to be lost in glioblastoma due to epigenetic silencing by methyl-CpG-binding domain protein 2 (MBD2). ADGRB1 inhibits angiogenesis through the release of N-terminal type-1 thrombospondin repeat fragments termed angiostatin.
Fig.1 EZH2 inhibitor EPZ-6438 retards medulloblastoma growth through epigenetic reactivation of tumor suppressor gene ADGRB1. (Purcell, 2017)
- Immune, Cardiac, and Pulmonary
Expression in immune tissue is a common feature for all five members of the ADGRE family (EMR1-4, CD97), two ADGRG receptors (GPR56, GPR97), and ADGRB1. In the central nervous system, ADGRB1 was shown to play a key role in the microglial clearance of dying neurons in collaboration with T-cell membrane protein 4 (TIM-4) and may also have a role in astrocytic phagocytosis. In the immune system, ADGRB1 is expressed in myeloid and lymphoid cells and has been implicated in innate and adaptive immune processes.
Fig.2 The BAI sub-family of adhesion GPCRs. (Purcell, 2017)
The aGPCRs are widely distributed and critical for many physiological processes, including cell adhesion, neural development, angiogenesis, and immune system function. Creative Biolabs has a team of professionals with a solid knowledge of gene therapy and is well-equipped to serve clients. These services include but are not limited to, vehicle development, potency tests, safety and toxicology analysis, and disease-specific gene therapy development solutions. Please feel free to contact us for more about your ADGRB1 project.
Reference
- Purcell, R. Activation and regulation of the brain-expressed adhesion G protein-coupled receptors ADGRB1/BAI1 and ADGRB2/BAI2: Implications for human disease. Diss. Emory University. 2017.
