Quantitative analysis of the native presynaptic cytomatrix by cryoelectron tomography.
The presynaptic terminal contains a complex network of filaments whose precise organization and functions are not yet understood. The cryoelectron tomography experiments reported in this study indicate that these structures play a prominent role in synaptic vesicle release. Docked synaptic vesicles did not make membrane to membrane contact with the active zone but were instead linked to it by tethers of different length. Our observations are consistent with an exocytosis model in which vesicles are first anchored by long (>5 nm) tethers that give way to multiple short tethers once vesicles enter the readily releasable pool. The formation of short tethers was inhibited by tetanus toxin, indicating that it depends on soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor complex assembly. Vesicles were extensively interlinked via a set of connectors that underwent profound rearrangements upon synaptic stimulation and okadaic acid treatment, suggesting a role of these connectors in synaptic vesicle mobilization and neurotransmitter release.
Fernández-Busnadiego
Rubén
R
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
Zuber
Benoît
B
Maurer
Ulrike Elisabeth
UE
Cyrklaff
Marek
M
Baumeister
Wolfgang
W
Lucic
Vladan
V
D000818:Animals; D055032:Electron Microscope Tomography; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000648:ultrastructure*; D046509:Tissue Culture Techniques