Biological complexity: controlling cell volume (Introduction)

by David Turell , Friday, August 17, 2018, 18:13 (2290 days ago) @ David Turell

A very complex molecular machine is unraveled:

https://www.sciencedaily.com/releases/2018/08/180816153144.htm

"Scientists at Scripps Research have solved the structure of a key protein that senses when our cells swell. This protein, called SWELL1 (or LRRC8A), works as an "ion channel" on the cell membrane to relieve pressure inside cells.

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"SWELL1 was discovered in 2014 in the lab of Ardem Patapoutian, PhD, professor at Scripps Research and investigator with the Howard Hughes Medical Institute. The discovery opened the door to crucial studies into how the protein functions.

"The next important step was to shed light on SWELL1's molecular structure. The scientists aimed to understand the basics of how this ion channel senses changes in volume. To do this, they needed to take a look at the channel's molecular machinery.

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"This new look at the ion channel suggests that interacting parts of the tendrils-sites that have a positive or a negative charge-sense a change in ionic strength in the cell (a dilution of the cell's salt contents as it absorbs water). The charged residues could send a signal up to the pore of the channel, telling the channel to release chloride ions from the cell and relieve the pressure.

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"Next, the researchers took a closer look at how the different parts of the SWELL1 structure affect channel function. They found that mutating the protein at either of two sites keeps the structure from properly controlling traffic through the ion channel.

"The new study shows bundles of the SWELL1 subunit alone-and scientists know that SWELL1 has to be there for a functional channel. But up to four other subunits can swap into the structure at different sites. Kefauver says the next step is to determine how different combinations of SWELL1 subunits come together to form ion channels with different activities."

Comment: be sure to look at the illustration to see the complexity of the molecular arrangement. The importance of volume maintenance cannot be underestimated, as cellular function can be damaged or destroyed under too much pressure. This mechanism had to be present in the first cells of life.