SYNAPTIC CLUSTERING OF THE CELL-ADHESION MOLECULE FASCICLIN-II BY DISCS-LARGE AND ITS ROLE IN THE REGULATION OF PRESYNAPTIC STRUCTURE

The cell adhesion molecule Fasciclin II (FASII) is involved in synapse development and plasticity. Here we provide genetic and biochemical e vidence that proper localization of FASII at type I glutamatergic syna pses of the Drosophila neuromuscular junction is mediated by binding b etween the intracellular tSXV bearing C-terminal tail of FASII and the PDZ1-2 domains of Discs-Large (DLG). Moreover, mutations in fasII and /or dig have similar effects on presynaptic ultrastructure, suggesting their functional involvement in a common developmental pathway. DLG c an directly mediate a biochemical complex and a macroscopic cluster of FASII and Shaker Kf channels in heterologous cells. These results ind icate a central role for DLG in the structural organization and downst ream signaling mechanisms of cell adhesion molecules and ion channels at synapses.