The pre-synaptic fusion machinery

Axel T Brunger; Ucheor B Choi; Ying Lai; Jeremy Leitz; Kristopher Ian White; Qiangjun Zhou

doi:10.1016/j.sbi.2019.03.007

The pre-synaptic fusion machinery

Curr Opin Struct Biol. 2019 Feb:54:179-188. doi: 10.1016/j.sbi.2019.03.007. Epub 2019 Apr 12.

Authors

Axel T Brunger¹, Ucheor B Choi², Ying Lai², Jeremy Leitz², Kristopher Ian White², Qiangjun Zhou²

Affiliations

¹ Department of Molecular and Cellular Physiology, Stanford University, Stanford, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, USA; Department of Structural Biology, Stanford University, Stanford, USA; Department of Photon Science, Stanford University, Stanford, USA; Howard Hughes Medical Institute, Stanford University, Stanford, USA. Electronic address: brunger@stanford.edu.
² Department of Molecular and Cellular Physiology, Stanford University, Stanford, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, USA; Department of Structural Biology, Stanford University, Stanford, USA; Department of Photon Science, Stanford University, Stanford, USA; Howard Hughes Medical Institute, Stanford University, Stanford, USA.

Abstract

Here, we review recent insights into the neuronal presynaptic fusion machinery that releases neurotransmitter molecules into the synaptic cleft upon stimulation. The structure of the pre-fusion state of the SNARE/complexin-1/synaptotagmin-1 synaptic protein complex suggests a new model for the initiation of fast Ca²⁺-triggered membrane fusion. Functional studies have revealed roles of the essential factors Munc18 and Munc13, demonstrating that a part of their function involves the proper assembly of synaptic protein complexes. Near-atomic resolution structures of the NSF/αSNAP/SNARE complex provide first glimpses of the molecular machinery that disassembles the SNARE complex during the synaptic vesicle cycle. These structures show how this machinery captures the SNARE substrate and provide clues as to a possible processing mechanism.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Calcium / metabolism
Humans
SNARE Proteins / metabolism
Synapses / metabolism*
Synaptic Vesicles / metabolism

Substances

SNARE Proteins
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding