4XHV

Crystal structure of Drosophila Spinophilin-PDZ and a C-terminal peptide of Neurexin

Summary for 4XHV

• Entry DOI: 10.2210/pdb4xhv/pdb
• Related: 3EGG
• Descriptor: LP20995p, Neurexin 1, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: spinophilin, neurexin, praesynaptic density, synapse, signaling protein
• Biological source: Drosophila melanogaster (Fruit fly); More
• Total number of polymer chains: 2
• Total formula weight: 11124.50

Authors

Driller, J.H.,Muhammad, K.G.H.,Reddy, S.,Rey, U.,Boehme, M.A.,Hollmann, C.,Ramesh, N.,Depner, H.,Luetzkendorf, J.,Matkovic, T.,Bergeron, D.,Quentin, C.,Schmoranzer, J.,Goettfert, F.,Holt, M.,Wahl, M.C.,Hell, S.W.,Walter, A.,Sigrist, S.J.,Loll, B. (deposition date: 2015-01-06, release date: 2015-07-01, Last modification date: 2024-01-10)

Primary citation

Muhammad, K.,Reddy-Alla, S.,Driller, J.H.,Schreiner, D.,Rey, U.,Bohme, M.A.,Hollmann, C.,Ramesh, N.,Depner, H.,Lutzkendorf, J.,Matkovic, T.,Gotz, T.,Bergeron, D.D.,Schmoranzer, J.,Goettfert, F.,Holt, M.,Wahl, M.C.,Hell, S.W.,Scheiffele, P.,Walter, A.M.,Loll, B.,Sigrist, S.J.
Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function.
Nat Commun, 6:8362-8362, 2015

PubMed 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.

PubMed: 26471740
DOI: 10.1038/ncomms9362

Experimental method

X-RAY DIFFRACTION (1.23 Å)