In overcrowded tissues, weaker cells are culled with a jolt of sodium. Understanding the mechanism might help treat asthma.
Epithelial cells working to extrude a cell from the tissue, a process by which overcrowded tissues remove excess or weakened cells to maintain a healthy barrier. Credit: Jody Rosenblatt.
Researchers at the Francis Crick Institute and King’s College London have uncovered a surprising role for electricity in keeping our body’s protective cell layers healthy, which could potentially protect against diseases such as asthma or cancer.
Cell biologist Jody Rosenblatt leads research teams at both King’s College London and the Crick. Her team studies how protective layers of cells called epithelial cells provide a stable barrier around our organs, and what a broken barrier means in diseases like asthma.
Over two decades ago, Jody and her team discovered what happens if this tightly packed layer of cells gets overcrowded – excess epithelial cells are ‘squeezed out’, causing them to die. Her lab and others found that this process of ‘extrusion’ is fundamental, common in living organisms from sea sponges to humans, yet some mysteries remain.
“We didn’t know how the body decides which cells are extruded – whether they are selected at random or if there is a more finely-tuned process,” says Jody.
To answer this question, as described in research published in Nature, Jody’s lab set up live imaging of overcrowded epithelial cells under a microscope, unsure of what they were going to see.
“When we watched the video, we saw a lightning-like flash from the epithelial cells before they extruded, some sort of weird contraction,” says Jody. “This was unexpected – we hadn’t fully appreciated the role of electricity. Typically, people think of the nerve cells as being positively and negatively charged – known as ‘polarised’ – but all our cells are.”
It takes a lot of energy to maintain these electric potentials – the ability to pass on a current from polarised segments of the cell – in cells like the epithelia. And for some energy-deficient cells, hiding in plain sight in the tissue, it’s simply too much.
“By blocking ion channels on the cell membranes in the lab, we found that overcrowding triggers sodium channels on epithelia to open, bringing in salts and depolarising the cells,” describes Jody. “The strong ones in the crowd can pump the sodium back out, repolarising themselves. But weak ones without enough energy can’t. They use a ‘last gasp’ of energy to activate a current that results in water rushing out of the cells, causing them to shrink and then extrude.”
Lead author Saranne Mitchell at King’s College London adds, “We see this sodium channel acting as a sensor, exposing cells with the least amount of energy and targeting those cells for death. This mechanism gives epithelia a constant surveillance system to rapidly detect weak cells and remove them. It’s like an electrical quality-control check, keeping tissues robust and functional.”
Previous research from Jody’s team highlighted how extrusion might be crucial to the treatments to repair the airway epithelial barrier in asthma, and their new findings today have opened even more doors to understanding additional diseases.
For example, Jody speculates that cancer cells might be able to hijack this process, allowing cells to overcrowd without extruding. Or energy depletion following a stroke, caused by impacted blood supply, might lead to excess extrusion and organ damage.
“Understanding this fundamental process means we can understand how lots of diseases involving epithelia develop, rather than a whack-a-mole approach for trying new treatments,” says Jody.
She concludes, “This is the beauty of fundamental cell biology. By keeping an open mind about what we see during live imaging, we can discover a surprising, but clearly critical, mechanism to keep tissue barriers happy and healthy.”
Adapted from an article from King’s College London.
