Organizing the synaptic junctions.

Synaptic adhesion molecules (SAMs) are essential for driving the formation, maturation, and plasticity of synaptic connections for neural networks. MAM domain-containing glycosylphosphatidylinositol anchors (MDGAs) are a type of SAM that regulates the formation of trans-synaptic bridges, which are critical for neurotransmission and synaptic differentiation. In a recent issue of the JBC, Lee et al. uncovered that MDGA1 can control protein-protein interactions and synaptic cleft activity by adopting different global 3D conformations. This novel molecular mechanism may be applicable to other SAMs that regulate protein-protein interactions and nanoscale organization in the synaptic cleft.