First atomic-scale ‘video’ of microtubules being assembled, a key process in cell division

Cells in the human body are constantly dividing. During each division, the genetic information contained in the chromosomes is duplicated, and each daughter cell receives a complete copy of the genetic material. This is a sophisticated process, a clockwork mechanism involving sophisticated and rapid changes within the cell. To make this possible, cells rely on microtubules, tiny structures that are actually tube-shaped. Understanding how they begin to form is a long-standing question.

Now, researchers from the Center for Genome Regulation (CRG), the Spanish National Cancer Research Center (CNIO), and the Spanish National Research Council (IBMB-CSIC) have decided to create the equivalent of a movie showing human biology. The first time I succeeded. Cells begin building microtubules.

The survey results are published in diary sciencesolving problems posed many years ago and laying the foundation for future breakthroughs in the treatment of diseases ranging from cancer to neurodevelopmental disorders.

long rope tearing chromosomes apart

Oscar Llorka, head of the CNIO’s Structural Biology Program and co-lead author of the study, explains what happens inside a cell when cell division begins: “When the chromosomes replicate their genetic information, they move to the center of the cell. And the cell, in a very surprising way, immediately puts out a big tube from each end of it, which hooks the chromosomes so that each It pulls the copies towards the opposite poles of the cell. Only then will it be possible to encapsulate copies of all our genetic material into each daughter cell.”

Microtubules are structures that shoot out “like long ropes that reach the chromosomes and divide them,” Jorca explains. “This is why microtubules are said to play an important role in cell division. We need to better understand the mechanisms that trigger the formation of these microtubules in the right place and at the right time. .”

These are also “cellular highways”

Microtubules are tubes that are one-thousandth of a millimeter long and nanometers in diameter. [millionths of a millimeter]. In addition to being key to cell division, they also act as “highways” for moving cellular components between different regions of the cell. They are also the structural elements that form the cells themselves, among other tasks. A better understanding of their formation has implications for multiple areas of biomedicine.

“Microtubules are important components of cells. Here we capture processes occurring within human cells. Given the fundamental role of microtubules in cell biology, this ultimately This could lead to new treatments for a wide range of diseases,” explains ICREA Research Professor Thomas. Surrey, CRG researcher and co-first author of the paper.

Molecular rings trigger microtubule formation

The high-resolution images obtained answer a long-standing question: how microtubule formation begins during the early stages of cell division.

We now know that it all begins when a complex structure made up of several proteins called “g TuRC” (pronounced “gamma-turk”) closes to form a ring.

g The shape of TuRC and its three-dimensional structure was discovered several years ago and surprised researchers. g TuRC was expected to be a closed ring that acts as a base mold on which microtubules are built. However, g TuRC appeared as an open ring. Its dimensions and shape were incompatible with those of the microtubule template.

New CRG and CNIO studies have revealed a mechanism by which g TuRC can close into a ring, effectively taking its full form and initiating microtubule formation. g TuRC closure occurs when the first molecular part of the microtubule attaches to it.

“This is the trick cells use to close the TuRC,” Lorca explains. “As soon as this first brick enters, the area of ​​g TuRC can hook it, acting as a latch that closes the ring like a loop and starts the process.”

To visualize this process, we needed to purify gTuRC from human cells and recapitulate the microtubule initiation process in vitro. The samples were viewed using a cryo-electron microscope, and artificial intelligence was used to analyze the data.