Journal
JOURNAL OF CELL BIOLOGY
Volume 221, Issue 5, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202108018
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Funding
- Intramural Research Program of the National Institutes of Health, National Cancer Institute
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Centrioles assembly is regulated by CPAP during the cell cycle, and insufficiency of CPAP can lead to incomplete microtubule triplets and fragmentation of centrioles. These findings improve our understanding of the role of CPAP in centrosome biogenesis and its association with human diseases.
Centrioles are structures that assemble centrosomes. CPAP is critical for centrosome assembly, and its mutations are found in patients with diseases such as primary microcephaly. CPAP's centrosomal localization, its dynamics, and the consequences of its insufficiency in human cells are poorly understood. Here we use human cells genetically engineered for fast degradation of CPAP, in combination with superresolution microscopy, to address these uncertainties. We show that three independent centrosomal CPAP populations are dynamically regulated during the cell cycle. We confirm that CPAP is critical for assembly of human centrioles, but not for recruitment of pericentriolar material on already assembled centrioles. Further, we reveal that CPAP insufficiency leads to centrioles with incomplete microtubule triplets that can convert to centrosomes, duplicate, and form mitotic spindle poles, but fragment owing to loss of cohesion between microtubule blades. These findings further our basic understanding of the role of CPAP in centrosome biogenesis and help understand how CPAP aberrations can lead to human diseases.
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