BAI2 is a G protein-coupled receptor that is expressed almost exclusively in the central nervous system. This receptor is highly expressed in astrocytes as well as in certain neuronal populations. A BAI2 mutation was recently identified by the NIH Undiagnosed Diseases Program as being associated with a novel neurological disorder. This disease-associated BAI2 mutation is a missense mutation that alters an amino acid in the receptor's cytoplasmic carboxyl-terminus, a region of BAI2 that is known to be important for controlling the receptor's signaling and regulation. In this project, we will assess the effects of the disease-associated mutation on the trafficking and signaling of BAI2 in order to determine how this mutation might be causing human disease and also gain insights into potential therapeutic options for patients harboring this mutation. Moreover, these studies will also shed significant light on the normal function of BAI2 and thereby set the stage for targeting this receptor pharmacologically in order to benefit the wider population of patients who express wild-type BAI2 but suffer from neurological or psychiatric disorders that might be treatable via modulation of BAI2 activity.
Disorders caused by single gene mutations can only be understood by understanding the consequences of the mutations on the functionality of the expressed proteins. This project is focused on studying a mutation in the G protein-coupled receptor BAI2 that is associated with a novel neurological disorder. We will assess the effects of the mutation on the trafficking and signaling of BAI2 to determine how this mutation may be causing human disease and provide insights into how patients harboring this mutation might be treated.
| Purcell, Ryan H; Toro, Camilo; Gahl, William A et al. (2017) A disease-associated mutation in the adhesion GPCR BAI2 (ADGRB2) increases receptor signaling activity. Hum Mutat 38:1751-1760 |
