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Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function

Muhammad, Karzan and Reddy-Alla, Suneel and Driller, Jan H. and Schreiner, Dietmar and Rey, Ulises and Böhme, Mathias A. and Hollmann, Christina and Ramesh, Niraja and Depner, Harald and Lützkendorf, Janine and Matkovic, Tanja and Götz, Torsten and Bergeron, Dominique D. and Schmoranzer, Jan and Goettfert, Fabian and Holt, Mathew and Wahl, Markus C. and Hell, Stefan W. and Scheiffele, Peter and Walter, Alexander M. and Loll, Bernhard and Sigrist, Stephan J.. (2015) Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function. Nature communications, 6. p. 8362.

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele)
UniBasel Contributors:Scheiffele, Peter
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:30 Jun 2016 11:00
Deposited On:22 Mar 2016 16:18

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