In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-10-25)
Abstract:
Cells in our body communicate by releasing compounds called transmitters that carry signals from one cell to the next. Packages called vesicles store transmitters within the signaling cell. When the cell needs to send a signal, the vesicles fuse with the cell's membrane and release their cargo. For many signaling processes, such as those used by neurons, this fusion is regulated, fast, and coupled to the signal that the cell receives to activate release. Specialized molecular machines made up of proteins and fatty acid molecules called signaling lipids enable this to happen. One signaling lipid called PI(4,5)P2 (short for phosphatidylinositol 4,5-bisphosphate) is essential for vesicle fusion as well as for other processes in cells. It interacts with several proteins that help it control fusion and the release of transmitter. While it is possible to study the role of these proteins using genetic tools to inactivate them, the signaling lipids are more difficult to manipulate. Existing methods result in slow changes in PI(4,5)P2 levels, making it hard to directly attribute later changes to PI(4,5)P2. Walter, Müller, Tawfik et al. developed a new method to measure how PI(4,5)P2 affects transmitter release in living mammalian cells, which causes a rapid increase in PI(4,5)P2 levels. The method uses a chemical compound called “caged PI(4,5)P2” that can be loaded into cells but remains undetected until ultraviolet light is shone on it. The ultraviolet light uncages the compound, generating active PI(4,5)P2 in less than one second. Walter et al. found that when they uncaged PI(4,5)P2 in this way, the amount of transmitter released by cells increased. Combining this with genetic tools, it was possible to investigate which proteins of the release machinery were required for this effect. The results suggest that two different types of proteins that interact with PI(4,5)P2 are needed: one must bind PI(4,5)P2 to carry out its role and the other helps PI(4,5)P2 accumulate at the site of vesicle fusion. The new method also allowed Walter et al. to show that a fast increase in PI(4,5)P2 triggers a subset of vesicles to fuse very rapidly. This shows that PI(4,5)P2 rapidly regulates the release of transmitter. Caged PI(4,5)P2 will be useful to study other processes in cells that need PI(4,5)P2, helping scientists understand more about how signaling lipids control many different events at cellular membranes.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.30203.001
DOI:
10.7554/eLife.30203.002
DOI:
10.7554/eLife.30203.003
DOI:
10.7554/eLife.30203.004
DOI:
10.7554/eLife.30203.005
DOI:
10.7554/eLife.30203.006
DOI:
10.7554/eLife.30203.007
DOI:
10.7554/eLife.30203.008
DOI:
10.7554/eLife.30203.009
DOI:
10.7554/eLife.30203.010
DOI:
10.7554/eLife.30203.011
DOI:
10.7554/eLife.30203.012
DOI:
10.7554/eLife.30203.013
DOI:
10.7554/eLife.30203.014
DOI:
10.7554/eLife.30203.015
DOI:
10.7554/eLife.30203.016
DOI:
10.7554/eLife.30203.017
DOI:
10.7554/eLife.30203.018
DOI:
10.7554/eLife.30203.019
DOI:
10.7554/eLife.30203.020
DOI:
10.7554/eLife.30203.021
DOI:
10.7554/eLife.30203.022
DOI:
10.7554/eLife.30203.023
DOI:
10.7554/eLife.30203.025
DOI:
10.7554/eLife.30203.026
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3
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