Essential protein to build and maintain the cellular skeleton

Microtubules are cell fibers that are part of the skeleton of the cell, called the “cytoskeleton”. They are essential for cells to maintain their shape, carry out their functions and be able to divide. Microtubules are fibers made up of units of a protein called “tubulin” and grow in length, incorporating new units of tubulin.

Scientists from the Barcelona Institute for Research in Biomedicine (IRB Barcelona), led by Dr. Jens Lüders, have discovered an essential role for the ch-TOG protein in the initiation of microtubule formation, specifically, in the phase of the cell cycle in which cells spend most of their time, which is interphase.

The cell cycle is made up of a series of stages that lead to the growth of the cell and the division into two daughter cells. The period between the moment a cell has just formed and when it is ready to divide is known as “interphase”. At interface, the cytoskeleton remains essential and plays a very active role in maintaining cell functions.

“The role of the ch-TOG protein in stimulating microtubule growth during cell division has already been described previously, but its role at the interface of human cells, that is, when cells are not dividing, was completely unknown. clear so far. Our work reveals that, in addition to contributing to the continued growth of the ends of the microtubules, this protein is key to initiating the formation of these fibers”, explains Dr. Lüders, head of the Microtubule Organization in Proliferation and Differentiation laboratory. IRB Barcelona cell phone.

Microscopy image of human cells with microtubules (in green) growing from the centrosome and from the Golgi apparatus (marked in red). (Image: IRB Barcelona)

The mechanism that the researchers have described is based on a transient binding of ch-TOG in the centrosome (one of the main places in the cell where microtubules are formed). The interaction of ch-TOG with a microtubule initiation center, the γTuRC complex, facilitates the binding of several tubulin molecules, and thus these fibers begin to form. Once they have started to form, ch-TOG is still attached to the end of the newly formed microtubule, which continues to grow as new tubulin molecules are incorporated.

For a long time, the scientific community has considered that the main function of ch-TOG was to elongate microtubules. However, this work supports the theory, which previous studies had already suggested in vitro and in other organisms, that ch-TOG is also essential in the initiation and formation of new microtubule fibers in humans.

“The ch-TOG protein has two regions; one grabs the tubulin molecules and the other binds to the microtubule, so that ch-TOG adds the tubulin to the fiber and thus it grows. What we have been able to observe is that the same two regions are also required for ch-TOG to bind to the tubulin complexes in the centrosomes and start adding tubulin, thus forming a new fiber from scratch,” explains Dr. Aamir Ali. , study co-author, formerly a postdoctoral researcher at IRB Barcelona and now in the Department of Biochemistry and Molecular Genetics at the University of Virginia School of Medicine, United States.

The researchers have also observed that, in human cells, the role of ch-TOG in initiating the formation of microtubule fibers is not only observed in the centrosome, but can also stimulate the initiation of these fibers from the surface of the centrosome. Golgi apparatus, another important point of microtubule assembly in certain types of cells.

The study is titled “Microtubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG”. And it has been published in the academic journal Nature Communications. (Source: IRB Barcelona)