Structural and Functional Basis of Cell-Adhesion and Signaling at the Synapse
Demet Arac, Ph.D.
Time: 22 Aralık 13:40; Place: FENS 2008
All functions of the brain require communication between neurons. Synaptic adhesion molecules are not only essential for the formation and maintenance of synaptic connections, but also are key molecules that mediate signaling between two neurons. First, we determined the crystal structure of the neuroligin/neurexincomplex, a synaptic adhesion complex involved in autism, and studied its function in synapse formation. Second, we focused on understanding the mechanism by which cell-adhesion type G protein coupled receptors (GPCRs) function in the brain. We discovered that all cell-adhesion GPCRs have a novelautoproteolytic domain that we termed the GPCR AutoproteolysisINducing (GAIN) domain.We determined the crystal structures of two GAIN domains and revealed the unique structural features that help mediate autoproteolysis. Strikingly, the GAIN domain is the locus of multiple human disease mutations and is evolutionarily conserved from tetrahymena and slime molds to mammals. In summary, our work redefined the cell-adhesion GPCR class, showing that members of this family share a large, unique and widespread autoproteolytic domain that is likely relevant for GPCR signaling and for multiple diseases of the brain.