In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-10-28)
Abstract:
The human nervous system contains billions of neurons that communicate with each other across junctions called synapses. When a neuron is activated, the levels of calcium ions inside the cell rise. This causes molecules called neurotransmitters to be released from the neuron at a synapse to make contact with the second neuron. The neurotransmitters are stored inside cells within compartments known as synaptic vesicles and are released when these vesicles fuse with the membrane surrounding the cell. Proteins called SNAREs regulate the membrane fusion process. These proteins assemble into bundles that help to drive vesicle and cell membranes together. Another protein called synaptotagmin-1 sticks out from the vesicle membrane and senses the levels of calcium ions in the cell to trigger membrane fusion at the right time. Synaptotagmin-1 has two regions that can bind to calcium ions, known as the C2 domains. When calcium ion levels rise, these domains insert into the cell membrane by binding to two fat molecules in the membrane called phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdInsP2). Synaptotagmin-1 also interacts with the SNARE proteins, but it is not known whether synaptotagmin-1 triggers fusion by binding directly to SNAREs, or by the way it inserts into the cell membrane. Pérez-Lara et al. used several biophysical methods to investigate how synaptotagmin-1 binds to PtdSer and PtdInsP2. The experiments show that these molecules bind to different regions of synaptotagmin-1 and work together to attach the protein to the cell membrane and insert the C2 domains. Calcium ions increase the affinity of synaptotagmin-1 binding to the cell membrane by making it harder for synaptotagmin-1 to separate from the membrane, rather than by increasing its ability to bind to it. Further experiments show that synaptotagmin-1 prefers to bind to membranes that contain PtdInsP2 over binding to the SNARE proteins. Together, the findings of Pérez-Lara et al. suggest that calcium ions may trigger the release of neurotransmitters by trapping synaptotagmin-1 at the cell membrane rather than by directly affecting how it interacts with SNARE proteins. Further work will be needed to establish exactly how the SNARE proteins, PtdInsP2 and synaptotagmin-1 interact.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.15886.001
DOI:
10.7554/eLife.15886.002
DOI:
10.7554/eLife.15886.003
DOI:
10.7554/eLife.15886.004
DOI:
10.7554/eLife.15886.005
DOI:
10.7554/eLife.15886.006
DOI:
10.7554/eLife.15886.007
DOI:
10.7554/eLife.15886.008
DOI:
10.7554/eLife.15886.009
DOI:
10.7554/eLife.15886.010
DOI:
10.7554/eLife.15886.011
DOI:
10.7554/eLife.15886.012
DOI:
10.7554/eLife.15886.013
DOI:
10.7554/eLife.15886.014
DOI:
10.7554/eLife.15886.015
DOI:
10.7554/eLife.15886.016
DOI:
10.7554/eLife.15886.017
DOI:
10.7554/eLife.15886.018
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
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