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Structural and Functional Studies of Latrophilin‐Family Adhesion G‐Protein Coupled Receptors
Author(s) -
Leon Katherine,
Lu Yue Christine,
Nazarko Olha,
Sando Richard,
Salzman Gabriel,
Südhof Thomas,
Araç Demet
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.664.7
Subject(s) - cell adhesion , g protein coupled receptor , receptor , fibronectin , microbiology and biotechnology , extracellular , transmembrane protein , adhesion , signal transduction , function (biology) , chemistry , transmembrane domain , cell adhesion molecule , extracellular matrix , biology , biochemistry , organic chemistry
Adhesion G‐protein coupled receptors (aGPCRs) contain uniquely large, autoproteolyzed extracellular regions that are involved in cell adhesion and may couple cellular adhesion to receptor signaling. The latrophilin (Lphn/ADGRL) family of aGPCRs has important roles in brain development, such as mediating interactions with fibronectin leucine‐rich repeat transmembrane proteins (FLRTs) in order to form synaptic junctions. There is growing interest in Lphns as promising drug targets because mutations in Lphns are associated with neurological disorders and cancers. To aid in this effort, we used structural and functional approaches to characterize Lphn ligand‐binding and signaling. We present the crystal structure of an extracellular fragment of Lphn3 in complex with FLRT3 and a model of the Lphn3/FLRT3/Uncoordinated‐5 trimeric complex, which provide insight into the role of cell‐adhesion proteins in synapse function. In addition, we developed a signaling assay to better understand the role of autoproteolysis in receptor function.