Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Fulltext
Final published version, 3.95 MB, PDF document
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.
Original language | English |
---|---|
Article number | 8362 |
Journal | Nature Communications |
Volume | 6 |
Number of pages | 15 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2015 |
Externally published | Yes |
- Animals, Cell Adhesion Molecules, Neuronal/metabolism, Drosophila, Drosophila Proteins/metabolism, Female, GTPase-Activating Proteins/metabolism, Male, Microfilament Proteins/metabolism, Nerve Tissue Proteins/metabolism, PDZ Domains, Synapses/metabolism
Research areas
ID: 334035837