Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function
Authors: Muhammad K, Reddy-Alla S, Driller JH, Schreiner D, Rey U, Böhme MA, Hollmann C, Ramesh N, Depner H, Lützkendorf J, Matkovic T, Götz T, Bergeron DD, Schmoranzer J, Goettfert F, Holt M, Wahl MC, Hell SW, Scheiffele P, Walter AM, Loll B, Sigrist SJ
CellNetworks People: Hell Stefan
Journal: Nat Commun. 2015 Oct 16;6:8362. doi: 10.1038/ncomms9362

Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis.