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

Author:

Wang Jennifer T1ORCID,Kong Dong23,Hoerner Christian R4,Loncarek Jadranka23,Stearns Tim15ORCID

Affiliation:

1. Department of Biology, Stanford University, Stanford, United States

2. Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, Frederick, United States

3. National Cancer Institute, National Institutes of Health, Frederick, United States

4. Division of Oncology, Department of Medicine, Stanford School of Medicine, Stanford, United States

5. Department of Genetics, Stanford School of Medicine, Stanford, United States

Abstract

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.

Funder

National Institute of General Medical Sciences

National Cancer Institute

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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