Os microtúbulos tripleto de centríolos são necessários na formação de centríolo estável e herança em células humanas

terça-feira, dezembro 12, 2017

Centriole triplet microtubules are required for stable centriole formation and inheritance in human cells

Jennifer T Wang Dong Kong Christian R Hoerner Jadranka Loncarek Tim Stearns Is a corresponding author

Stanford University, United States Center for Cancer Research, United States National Cancer Institute, National Institutes of Health, United States Stanford School of Medicine, United States



Centrioles are composed of long-lived microtubules arranged in nine triplets. However, the contribution of triplet microtubules to mammalian centriole formation and stability is unknown. Little is known of the mechanism of triplet microtubule formation, but experiments in unicellular eukaryotes indicate that delta-tubulin and epsilon-tubulin, two less-studied tubulin family members, are required. Here, we report that centrioles in delta-tubulin and epsilon-tubulin null mutant human cells lack triplet microtubules and fail to undergo centriole maturation. These aberrant centrioles are formed de novo each cell cycle, but are unstable and do not persist to the next cell cycle, leading to a futile cycle of centriole formation and disintegration. Disintegration can be suppressed by paclitaxel treatment. Delta-tubulin and epsilon-tubulin physically interact, indicating that these tubulins act together to maintain triplet microtubules and that these are necessary for inheritance of centrioles from one cell cycle to the next.

eLife digest

Most structures inside a cell have a short lifespan and are continually replaced. Centrioles – specialized structures that help cells divide, and send and receive signals – are among the few exceptions and can persist through many cell generations. Centrioles are cylindrical structures that are made up of protein tubes called microtubules. Specifically, nine groups of three microtubules, known as triplet microtubules, are linked together to make the walls of the cylinder. The triplets of microtubules are only found in centrioles, and until now it was not known what role this specific formation plays.

Now, Wang et al. studied two lesser known members of the protein family that build the microtubules, called delta-tubulin and epsilon-tubulin. When either of these proteins was removed from human cells grown in the laboratory, the centrioles only had single microtubules rather than the usual triplets. The centrioles still formed at the correct time, but disappeared soon after the cell had divided.

When the cells were then treated with a drug that stabilizes the microtubules, the centrioles no longer disappeared once the cell had divided. This suggests that the triplet microtubule formation is needed to stabilize and maintain the centrioles through the cell divisions. Moreover, the results were similar for delta- and epsilon-tubulin, and it appears that the proteins work together to help stabilize the triplet microtubules.

Defects in centrioles are associated with many diseases, including some types of cancer and many genetic conditions that can lead to heart or kidney disease, obesity, diabetes and many others. Deeper knowledge of centriole structure and its role may help us to better understand these diseases.