Red blood cell formation requires a surprise protein!

Red blood cell formation requires a surprise protein!

Every cell in the body, whether skin or muscle or brain, starts out as a generic cell that acquires its unique characteristics after undergoing a process of specialization. Nowhere is this process more dramatic than it is in red blood cells.

In order to make as much room as possible for the oxygen-carrying protein hemoglobin, pretty much everything else inside these precursor red blood cells--nucleus, mitochondria, ribosomes and more--gets purged. Jam-packing red blood cells with hemoglobin is essential. Doing so ensures that all the body's tissues and organs are well nourished with oxygen to carry on their normal functions.

But how does this cell remodeling take place to begin with?

Researchers now have identified the mechanism behind red blood cell specialization and revealed that it is controlled by an enzyme. Their findings, published in the journal Science, could spark the development of new treatments for blood disorders and cancers.

"The creation of highly specialized cells is very important for processes such as oxygen delivery to tissues, our ability to see and reproduce, and to make skin," senior author said. "Understanding exactly how this happens gives us better insight into some of the most fundamental properties of living things."

During cell specialization, unwanted parts of a generic, immature cell are removed by the proteasome, protein-gobbling strings of molecules, or the cells' "trash compactors," says study first author.

The researchers set out to find the mechanism that controls which parts get destroyed and which parts are spared before the precursor red blood cell becomes a full-fledged one.

The UBE2O enzyme marks cell parts for destruction by tagging them with a small protein called ubiquitin. This tagging allows the proteasome to recognize cells destined for destruction. The vast machinery, known as the ubiquitin-proteasome system (UPS), is switched on constantly throughout the body to remove unnecessary proteins and keep cells free of clutter.

Previously, UPS had not been linked to the specialization of red blood cells. Researchers noticed large amounts of the enzyme present in immature red blood cells. That was a powerful clue. The combination of UBE2O's pronounced presence and its known function as cellular debris-remover made it a promising candidate for the role of a key regulator of cell specialization.

The researchers observed that mice without the enzyme were anemic, a marker of red blood cell deficiency. The observation supported the notion that UBE2O may play a role in red blood cell development.

Using a series of tests that relied on large-scale protein analyses not available in earlier decades, the researchers confirmed the enzyme's role. Their results revealed that immature red blood cells lacking UBE2O retained hundreds of proteins and failed to become specialized.

The researchers also demonstrated that when isolated from immature red blood cells and tested in other cell types, UBE2O still marked the right proteins for destruction, suggesting that the enzyme is the primary regulator of red blood cell specialization.

The researchers have yet to determine whether the mechanism they found in red blood cells controls specialization of other cells as well.

Because the enzyme plays an important role in the development of red blood cells, the researchers say they hope their work could lead to therapies for certain blood disorders and blood cancers. The present study revealed that, in mice, UBE2O deficiency powerfully suppressed the symptoms of a blood disorder known as beta thalassemia.