Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function
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Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function. / Muhammad, Karzan; Reddy-Alla, Suneel; Driller, Jan H; Schreiner, Dietmar; Rey, Ulises; Böhme, Mathias A; Hollmann, Christina; Ramesh, Niraja; Depner, Harald; Lützkendorf, Janine; Matkovic, Tanja; Götz, Torsten; Bergeron, Dominique D; Schmoranzer, Jan; Goettfert, Fabian; Holt, Mathew; Wahl, Markus C; Hell, Stefan W; Scheiffele, Peter; Walter, Alexander M; Loll, Bernhard; Sigrist, Stephan J.
In: Nature Communications, Vol. 6, 8362, 2015.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function
AU - Muhammad, Karzan
AU - Reddy-Alla, Suneel
AU - Driller, Jan H
AU - Schreiner, Dietmar
AU - Rey, Ulises
AU - Böhme, Mathias A
AU - Hollmann, Christina
AU - Ramesh, Niraja
AU - Depner, Harald
AU - Lützkendorf, Janine
AU - Matkovic, Tanja
AU - Götz, Torsten
AU - Bergeron, Dominique D
AU - Schmoranzer, Jan
AU - Goettfert, Fabian
AU - Holt, Mathew
AU - Wahl, Markus C
AU - Hell, Stefan W
AU - Scheiffele, Peter
AU - Walter, Alexander M
AU - Loll, Bernhard
AU - Sigrist, Stephan J
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Adhesion Molecules, Neuronal/metabolism
KW - Drosophila
KW - Drosophila Proteins/metabolism
KW - Female
KW - GTPase-Activating Proteins/metabolism
KW - Male
KW - Microfilament Proteins/metabolism
KW - Nerve Tissue Proteins/metabolism
KW - PDZ Domains
KW - Synapses/metabolism
U2 - 10.1038/ncomms9362
DO - 10.1038/ncomms9362
M3 - Journal article
C2 - 26471740
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 8362
ER -
ID: 334035837