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PDBsum entry 4xhv
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Signaling protein
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PDB id
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4xhv
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References listed in PDB file
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Key reference
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Title
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Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function.
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Authors
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K.Muhammad,
S.Reddy-Alla,
J.H.Driller,
D.Schreiner,
U.Rey,
M.A.Böhme,
C.Hollmann,
N.Ramesh,
H.Depner,
J.Lützkendorf,
T.Matkovic,
T.Götz,
D.D.Bergeron,
J.Schmoranzer,
F.Goettfert,
M.Holt,
M.C.Wahl,
S.W.Hell,
P.Scheiffele,
A.M.Walter,
B.Loll,
S.J.Sigrist.
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Ref.
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Nat Commun, 2015,
6,
8362.
[DOI no: ]
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PubMed id
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Abstract
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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.
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