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CPAP insufficiency leads to incomplete centrioles that duplicate but fragment
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2022-04-11 , DOI: 10.1083/jcb.202108018
Alejandra Vásquez-Limeta 1 , Kimberly Lukasik 1 , Dong Kong 1 , Catherine Sullenberger 1 , Delgermaa Luvsanjav 1 , Natalie Sahabandu 1 , Raj Chari 2 , Jadranka Loncarek 1
Affiliation  

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.

中文翻译:

CPAP 不足会导致中心粒不完整,复制但碎片

中心粒是组装中心体的结构。CPAP 对于中心体组装至关重要,其突变存在于患有原发性小头畸形等疾病的患者中。CPAP 的中心体定位、其动态以及其在人类细胞中的不足的后果人们知之甚少。在这里,我们使用经过基因工程改造的人类细胞来快速降解 CPAP,并结合超分辨率显微镜来解决这些不确定性。我们发现三个独立的中心体 CPAP 群体在细胞周期中受到动态调节。我们确认,CPAP 对于人类中心粒的组装至关重要,但对于在已组装的中心粒上招募中心粒周围材料则不然。此外,我们发现,CPAP 不足会导致中心粒具有不完整的微管三联体,这些三联体可以转化为中心体、复制并形成有丝分裂纺锤体极,但由于微管叶片之间的内聚力丧失而碎片。这些发现进一步加深了我们对 CPAP 在中心体生物发生中的作用的基本了解,并有助于了解 CPAP 畸变如何导致人类疾病。
更新日期:2022-04-11
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