SNARE complex oligomerization by synaphin/complexin is essential for synaptic vesicle exocytosis.
Synaphin/complexin is a cytosolic protein that preferentially binds to syntaxin within the SNARE complex. We find that synaphin promotes SNAREs to form precomplexes that oligomerize into higher order structures. A peptide from the central, syntaxin binding domain of synaphin competitively inhibits these two proteins from interacting and prevents SNARE complexes from oligomerizing. Injection of this peptide into squid giant presynaptic terminals inhibited neurotransmitter release at a late prefusion step of synaptic vesicle exocytosis. We propose that oligomerization of SNARE complexes into a higher order structure creates a SNARE scaffold for efficient, regulated fusion of synaptic vesicles.
Tokumaru
H
H
Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA.
Umayahara
K
K
Pellegrini
L L
LL
Ishizuka
T
T
Saisu
H
H
Betz
H
H
Augustine
G J
GJ
Abe
T
T
D000200:Action Potentials; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D049832:Decapodiformes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D004594:Electrophysiology; D005089:Exocytosis; D007700:Kinetics; D008565:Membrane Proteins / Q000494:pharmacology / Q000502:physiology*; D008854:Microscopy, Electron; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D050600:SNARE Proteins; D017386:Sequence Homology, Amino Acid; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013997:Time Factors; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D011994:Recombinant Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; C095992:complexin I; C095993:complexin II