Science and Technology Daily, Beijing, February 1 (Reporter Zhang Jiaxin) A team from the Center for Genomic Regulation in Barcelona, Spain, and the Spanish National Cancer Research Center captured the world's first high-resolution image of the earliest moments of microtubule formation in human cells. The discovery, published in the journal Science on the 1st, lays the foundation for treating many different types of diseases, from cancer to neurodevelopmental disorders.
In neurons, microtubules are like "highways" for long-distance transport of cellular molecules. Microtubules are assembled by the γ-tubulin ring complex (γ-TuRC). These proteins act like a blueprint, placing tubulin in a specific order, a process called microtubule nucleation.
For cells to work properly, microtubules need to be made of 13 different tubulin proteins. A few years ago, researchers were puzzled to discover that human gamma-TuRC exposed 14 tubulins, but high-resolution structural imaging of all tubulins has been elusive.
To observe gamma-TuRC as it formed microtubules, the researchers prepared samples at the center of an electron microscope and flash-frozen them in a thin layer of ice to preserve the natural shape of the molecules involved to help discern near-atomic-scale structures. detail. The researchers then used cryo-electron microscopy and sophisticated image processing methods to determine the three-dimensional structure of γ-TuRC during the formation of microtubules.
The analysis showed that γ-TuRC subtly changes shape as it begins the nucleation process and begins to form microtubules. It is initially open and gradually closes as microtubules grow. This change causes γ-TuRC to hide one of its 14 microtubules, creating a structure with only 13 microtubules.
The best-known consequence of microtubule dysfunction is cancer, a disease characterized by uncontrolled cell proliferation. When something goes wrong with the microtubule-forming process, neurodevelopmental disorders such as microcephaly can occur, as well as other conditions ranging from respiratory disorders to heart disease.
Some cancer drugs work by targeting microtubules, preventing them from breaking down or forming in the first place. However, these drugs indiscriminately destroy microtubules in cancer cells and healthy cells, causing side effects and tumors becoming resistant to these drugs. Understanding the precise mechanisms of microtubule laying will help develop more targeted and effective cancer treatments.