Complexins regulate a late step in Ca2+-dependent neurotransmitter release.
Synaptic vesicle fusion at synapses is triggered by increases in cytosolic Ca2+ levels. However, the identity of the Ca2+ sensor and the transduction mechanism of the Ca2+ trigger are unknown. We show that Complexins, stoichiometric components of the exocytotic core complex, are important regulators of transmitter release at a step immediately preceding vesicle fusion. Neurons lacking Complexins show a dramatically reduced transmitter release efficiency due to decreased Ca2+ sensitivity of the synaptic secretion process. Analyses of mutant neurons demonstrate that Complexins are acting at or following the Ca2+-triggering step of fast synchronous transmitter release by regulating the exocytotic Ca2+ sensor, its interaction with the core complex fusion machinery, or the efficiency of the fusion apparatus itself.
Reim
K
K
Max-Planck-Institut für Experimentelle Medizin, Abteilung Neurogenetik, AG Molekulare Neurobiologie, Hermann-Rein-Str. 3, D-37075 Göttingen, Bundesrepublik, Deutschland.
Mansour
M
M
Varoqueaux
F
F
McMahon
H T
HT
Südhof
T C
TC
Brose
N
N
Rosenmund
C
C
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017353:Gene Deletion; D006624:Hippocampus / Q000166:cytology; D007476:Ionophores / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology
D033942:Adaptor Proteins, Vesicular Transport; D007476:Ionophores; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C095992:complexin I; C095993:complexin II; D000001:Calcimycin; D002118:Calcium