Protein That Bonds Cells Also Helps Them Swallow Dead Neighbors, Study Finds

Researchers have found that E-cadherin, which is usually thought of as the adhesive that holds cells and tissues together, actually has another role: it helps epithelial cells take in nearby dead cells. The study, published in Nature Communications, demonstrates that the very molecular tools that seal the body’s surfaces are reused to get rid of cellular waste.

Verena Ruprecht, an ICREA Research Professor, led the study. She had previously shown that embryos employ epithelial tissues to collectively eliminate dying cells as a primary means of self-protection. Her team observed living zebrafish and mouse embryos to witness the process at work.

The Glue That Holds Tissues Together

E-cadherin belongs to a bigger molecular system that holds together the cells lining the skin, gut and airways. Every cell bonds with E-cadherin molecules on its neighbors, which gives these tissues their strength so they stay whole. The new study shows that this very machinery comes together right at the point where a dying cell meets the tissue.

The researchers ran two tests to see if E-cadherin binds to a dying cell the same way it binds neighboring epithelial cells. In the first test, they exposed the tissue to dying cells that had been stripped of E-cadherin. The epithelial tissue still removed those cells just as well as it did normal dying cells. In the second test, they added fat droplets that carried a signal usually found on dying cells but contained no protein at all. The cells still engulfed those droplets.

How Cells Eat Without Breaking the Barrier

A cell absorbing something close to its own size presents a physical problem. Cells lining surfaces sit closely together, forming barriers that must remain sealed, even as individual cells bend their shape to get rid of waste.

A live imaging study showed that an epithelial cell’s two sides act independently of each other. The underside stretches and bends to wrap around a dead cell, whereas the top side stays largely the same. That top surface keeps up the tissue barrier, and measurements showed its area hardly changed before, during or after the engulfment. The underside was the one that suffered significant distortion during the entire process.

The cell behavior resembles dancers linked arm-in-arm, whose upper bodies stay calm even as their feet carry out ever more intricate steps whenever a cell near them dies, according to Ruprecht. “It’s the same dancer with a different choreography,”

A Rope and a Brake

The mechanics behind the cleanup were also explored by the researchers. A single protein within the E-cadherin complex served as a rope, joining the molecular assembly to the cell’s inner skeleton and permitting force to pass across the surface of the material being engulfed. Without this tethering protein, or without the specific region that links it to the skeleton, cells lost their ability to take in dead cells.

The cell’s contractile machinery had another component acting as a brake, and removing that brake did not improve the cleanup process. The cell instead became too rigid, losing its capacity to properly remove dying cells.

The Process Extends Beyond Zebrafish

After studying zebrafish, the researchers turned their attention to other species to see if the mechanism applies more widely. Early-stage mouse embryos were found to behave similarly when E-cadherin was blocked: dying cells stayed uncleared. This result echoes what was observed in zebrafish, pointing toward a shared mechanism across vertebrates.

What Happens in Adults?

One open question concerns whether the same E-cadherin-dependent mechanism works in adult zebrafish or mice, or in any kind of human tissue. There are grounds for believing it might. Adult epithelial tissues already dispose of dying cells in several places:

• The retina
• The colon
• The airways
• The mammary gland

E-cadherin is present throughout epithelial tissues in the body, and its structure has stayed very much the same across species.

Dead cells that stay put inside body tissues are a source of trouble. They cause lasting irritation, and learning how the body gets rid of them might show us more about what goes wrong when the system stops working right.

The trick relies on a clear split of duties between two parts of the cell. One surface remains closed off, while the other bends. Force travels along the rope, and the brake keeps the cell from bending too far. It reads like steps in a dance, carried out at a scale too small for the human eye to catch.

Scientists are still working to piece together the complete picture of how this system operates in grown people. The building blocks are present, though: a protein found throughout the body, a familiar task of clearing waste, and a process that has remained steady across species for a very long time.

Source material: “The “glue” holding your cells together has a surprising second job,” ScienceDaily.

biology · cadherin · cells · cellular biology · science