A Comprehensive Mutagenesis Screen of the Adhesion GPCR Latrophilin-1/ADGRL1.
作者： Olha Nazarko , Amanuel Kibrom , Jana Winkler , Katherine Leon , Hannah Stoveken
DOI: 10.1016/J.ISCI.2018.04.019
关键词:
摘要: Adhesion G-protein-coupled receptors (aGPCRs) play critical roles in diverse cellular processes neurobiology, development, immunity, and numerous diseases. The lack of molecular understanding their activation mechanisms, especially with regard to the transmembrane domains, hampers further studies facilitate aGPCR-targeted drug development. Latrophilin-1/ADGRL1 is a model aGPCR that regulates synapse formation embryogenesis, its mutations are associated cancer attention-deficit/hyperactivity disorder. Here, we established functional assays monitor latrophilin-1 function showed by endogenous agonist peptide. Via comprehensive mutagenesis screen, identified domain residues essential for basal activity peptide response. Strikingly, cancer-associated mutation exhibited increased failed rescue embryonic developmental phenotype transgenic worms. These results provide mechanistic foundation future design.
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