Department of Cell and Developmental Biology, Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, France.
Aix-Marseille Univ, CNRS, IBDM, Marseille, France.
Dev Biol. 2021 Mar;471:10-17. doi: 10.1016/j.ydbio.2020.11.011. Epub 2020 Dec 4.
Centriole amplification in multiciliated cells occurs in a pseudo-cell cycle regulated process that typically utilizes a poorly characterized molecularly dense structure called the deuterosome. We identified the centrosomal protein Cep70 as a novel deuterosome-associated protein that forms a complex with other deuterosome proteins, CCDC78 and Deup1. Cep70 dynamically associates with deuterosomes during centriole amplification in the ciliated epithelia of Xenopus embryos. Cep70 is not found in nascent deuterosomes prior to amplification. However, it becomes localized at deuterosomes at the onset of centriole biogenesis and remains there after the completion of centriole amplification. Deuterosome localization requires a conserved C-terminal "Cep70" motif. Depletion of Cep70 using morpholino oligos or CRISPR/Cas9 editing in F0 embryos leads to a severe decrease in centriole formation in both endogenous MCCs, as well as ectopically induced MCCs. Consistent with a decrease in centrioles, endogenous MCCs have defects in the process of radial intercalation. We propose that Cep70 represents a novel regulator of centriole biogenesis in MCCs.
中心体扩增发生在多纤毛细胞的伪细胞周期调控过程中，该过程通常利用一种特征不明显的分子密集结构，称为后致密体。我们鉴定出中心体蛋白 Cep70 是一种新的后致密体相关蛋白，它与其他后致密体蛋白 CCDC78 和 Deup1 形成复合物。在非洲爪蟾胚胎纤毛上皮的中心体扩增过程中，Cep70 与后致密体动态结合。在扩增之前，Cep70 不存在于新生的后致密体中。然而，它在中心体发生的起始时定位在后致密体上，并在中心体扩增完成后仍保留在那里。后致密体的定位需要保守的 C 末端“Cep70”基序。在 F0 胚胎中使用 MO 寡核苷酸或 CRISPR/Cas9 编辑敲低 Cep70，会导致内源性多纤毛细胞以及异位诱导的多纤毛细胞中中心体形成严重减少。与中心体减少一致，内源性多纤毛细胞在放射状插入过程中存在缺陷。我们提出 Cep70 代表多纤毛细胞中中心体发生的新型调节因子。
