Uncoupling the roles of synaptotagmin I as a dual Ca2+ sensor during endo- and exocytosis of synaptic vesicles

@article{Yao2012UncouplingTR,
  title={Uncoupling the roles of synaptotagmin I as a dual Ca2+ sensor during endo- and exocytosis of synaptic vesicles},
  author={Jun Yao and Sung E. Kwon and Jon D. Gaffaney and F. Mark Dunning and Edwin R. Chapman},
  journal={Nature neuroscience},
  year={2012},
  volume={15},
  pages={243 - 249}
}
Synaptotagmin I (syt1) is required for normal rates of synaptic vesicle endo- and exocytosis. However, whether the kinetic defects observed during endocytosis in Syt1 knockout neurons are secondary to defective exocytosis or whether syt1 directly regulates the rate of vesicle retrieval remains unknown. To address this question, we sought to dissociate these two activities. We uncoupled the function of syt1 in exo- and endocytosis in mouse neurons either by re-targeting the protein or via… 

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References

SHOWING 1-10 OF 52 REFERENCES

Synaptotagmin I is necessary for compensatory synaptic vesicle endocytosis in vivo

It is demonstrated that Syt I is necessary for the endocytosis of synaptic vesicles that have undergone exocytotic treatment using a functional SyT I protein.

Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I.

It is shown that endocytosis is significantly impaired in the absence of SytI with the relative rates of endocytic-endocytic coupling in synapses reduced approximately 3-fold with respect to WT.

Three distinct kinetic groupings of the synaptotagmin family: candidate sensors for rapid and delayed exocytosis.

Results indicate that syts have diverged to release Ca2+ and membranes with distinct kinetics, and isoforms of syt, which have much slower disassembly kinetics than does syt I, might function as Ca 2+ sensors for asynchronous release, which occurs after Ca2- domains have collapsed.

The tandem C2 domains of synaptotagmin contain redundant Ca2+ binding sites that cooperate to engage t-SNAREs and trigger exocytosis

It is concluded that synaptotagmin–SNARE interactions regulate membrane fusion and that cooperation between synaptoagmin's C2 domains is crucial to its function.

The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo

It is shown that mutating two of the Ca2-binding aspartate residues in the C2B domain of synaptotagmin decreased evoked transmitter release by >95%, and decreased the apparent Ca2+ affinity of evoked transmitters release.

Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals

Molecular basis of synaptic vesicle cargo recognition by the endocytic sorting adaptor stonin 2

The data identify the molecular determinants for recognition of synaptotagmin by stonin 2 or its Caenorhabditis elegans orthologue UNC-41B and suggest that the mechanism of stonIn-mediated SV cargo recognition is conserved from worms to mammals.
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