A research team discovers the enzyme that allows actin to become functional

Actin: an important protein for cell architecture and movement

Actin is a globular protein, i.e. a protein having an essentially spherical structure. The actin molecule is approximately 5.45 nanometers in diameter and contains 375 amino acids, one of which is modified.

In humans, actin is an important protein since we produce up to 100 kg of it during our lifetime. It is one of the essential components of our cells where it plays many roles. It gives cells their shape and allows cell maintenance by playing the role of cytoskeleton. It is involved in the phenomenon of muscle contraction and plays an important role in allowing the separation of daughter cells resulting from cell division. It is also actin which allows the microvilli of the epithelial cells of the intestine to maintain themselves and it is also actin which allows the amoeba and certain white blood cells to carry out phagocytosis.

In the cell, actin exists in two forms: G-actin and F-actin. G-actin is the globular protein that is water-soluble. F-actin or filamentous actin is nothing but a polymer of G-actin.

In humans and other mammals, there are also several isoforms of this protein. The isoforms of a protein represent the different forms that a protein, however, produced by the same gene can take.

Actin is found in virtually every cell in the body, but in greater amounts in striated smooth muscle, skeletal striated muscle, and cardiac muscle. Actin is a very well conserved protein that is found in animal and human cells as well as in bacteria or yeasts.

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A fluorescent antibody

actin

This drawing shows the actin microfilaments involved in maintaining the cell cytoskeleton. Credits: VectorMine/Shutterstock

Because of its importance in cells, researchers have long been interested in actin and know a great deal about this essential protein. They know that like many proteins, actin molecules need to be stripped of a specific amino acid soon after they form in order to do their job properly. Scientists know which amino acid is removed and which side of the molecule it is on. On the other hand, they ignore the enzyme which intervenes in this process.

Scientists from the Netherlands Cancer Institute have just found the gene that until now has been considered mysterious and is responsible for the synthesis of this enzyme. Using haploid cells, i.e. cells that have only one set of chromosomes instead of two, the researchers caused random mutations within their DNA, which resulted in produce a whole bunch of cells carrying different mutations. To select cells with mutations in the genes coding for actin and therefore having produced a defective protein, the scientists added an antibody labeled with a fluorescent substance to the cells in culture. Since the scientists know the amino acid that is removed during protein maturation, they were able to create a labeled antibody specifically directed against that amino acid. Fluorescence makes it possible to select cells producing immature actin.

After having selected the right cells, it still remained to determine the gene or genes involved in the synthesis of the enzyme which removes this amino acid to make actin functional.

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A pair of molecular scissors to cut a specific amino acid

During its work, the team of scientists finally discovered that a hitherto unknown gene and with which no researcher has ever worked intervenes in the synthesis of an enzyme which acts like a pair of molecular scissors cutting the immature actin protein in the right place to remove the right amino acid. The researchers named this gene ACTMAP for ACTin Maturation Protease.

In order to control the effects of the absence of the ACTMAP gene in living beings, the scientists used mice. They quickly realized that rodents that lack this gene have incomplete skeletal cells. This does not compromise their survival, but leads to many problems with muscle weakness.

This is not the first time that this team has discovered a gene that codes for an enzyme that acts as molecular scissors. Some time ago, they identified three other enzymes involved in the removal of an amino acid from another component of the cell skeleton, tubulin. Thanks to these enzymes, tubulin can properly perform its functions within the cell.

With this discovery, the team of Dutch researchers has made it possible to complete knowledge of the cellular skeleton, which could in the future open the way to treatments for certain diseases. They do not intend to stop there and still hope to one day be able to determine the function of our 23,000 genes. And it is not the work that is lacking since to date, scientists know the function of about half of them.

Read also: How many genes are there in the human genome?

Source

Peter Haahr, Ricardo A. Galli, Lisa G. van den Hengel, Onno B. Bleijerveld, Justina Kazokaitė-Adomaitienė, Ji-Ying Song, Lona J. Kroese, Paul Krimpenfort, Marijke P. Baltissen, Thijn R. Brummelkamp, ​​“Actin maturation requires the ACTMAP/C19orf54 protease”, Science29 Sep 2022, Vol 377, Issue 6614, https://www.science.org/doi/10.1126/science.abq5082

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