Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function
| Autor: | Fabian Goettfert, Stephan J. Sigrist, Markus C. Wahl, Suneel Reddy-Alla, Ulises Rey, Karzan Muhammad, Bernhard Loll, Peter Scheiffele, Jan Schmoranzer, Niraja Ramesh, Mathias A. Böhme, Alexander M. Walter, Jan H. Driller, Dietmar Schreiner, Dominique Dufour Bergeron, Torsten W.B. Götz, Tanja Matkovic, Janine Lützkendorf, Harald Depner, Christina Hollmann, Stefan W. Hell, Matthew Holt |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Scaffold protein
Male GTPase-activating protein Cell Adhesion Molecules Neuronal Neurexin General Physics and Astronomy PDZ Domains Neuroligin Nerve Tissue Proteins Biology General Biochemistry Genetics and Molecular Biology Exocytosis Neuromuscular junction Article medicine Animals Drosophila Proteins Active zone Multidisciplinary integumentary system GTPase-Activating Proteins Microfilament Proteins fungi General Chemistry Cell biology Signalling medicine.anatomical_structure Synapses Drosophila Female |
| Zdroj: | Nature Communications, 6: 8362 Nature Communications |
| Popis: | 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. Synaptic assembly depends on trans-synaptic Neurexin/Neuroligin signalling. Here, Muhammad et al. show that Spinophilin, a pre-synaptic scaffolding protein, interacts with Neurexin, in competition with Syd-1, to regulate the formation and function of synaptic active zones at Drosophila neuromuscular junctions. |
| Databáze: | OpenAIRE |
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