Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, China.
State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing 100871, China.
Nat Commun. 2017 Apr 19;8:15057. doi: 10.1038/ncomms15057.
In animal cells, the centrosome is the main microtubule-organizing centre where microtubules are nucleated and anchored. The centriole subdistal appendages (SDAs) are the key structures that anchor microtubules in interphase cells, but the composition and assembly mechanisms of SDAs are not well understood. Here, we reveal that centrosome-binding proteins, coiled-coil domain containing (CCDC) 120 and CCDC68 are two novel SDA components required for hierarchical SDA assembly in human cells. CCDC120 is anchored to SDAs by ODF2 and recruits CEP170 and Ninein to the centrosome through different coiled-coil domains at its N terminus. CCDC68 is a CEP170-interacting protein that competes with CCDC120 in recruiting CEP170 to SDAs. Furthermore, CCDC120 and CCDC68 are required for centrosome microtubule anchoring. Our findings elucidate the molecular basis for centriole SDA hierarchical assembly and microtubule anchoring in human interphase cells.
在动物细胞中,中心体是微管的主要组织中心,微管在这里起始和锚定。中心粒亚末端附属物(SDAs)是锚定有丝分裂细胞中微管的关键结构,但 SDAs 的组成和组装机制尚不清楚。在这里,我们揭示了中心体结合蛋白,卷曲螺旋域包含(CCDC)120 和 CCDC68 是两种新型的 SDA 组成部分,它们在人类细胞中分层 SDA 组装中是必需的。CCDC120 通过 ODF2 锚定在 SDAs 上,并通过其 N 端的不同卷曲螺旋结构域将 CEP170 和 Ninein 募集到中心体。CCDC68 是 CEP170 的相互作用蛋白,它与 CCDC120 竞争,将 CEP170 募集到 SDAs。此外,CCDC120 和 CCDC68 对于中心体微管锚定是必需的。我们的发现阐明了人类有丝分裂细胞中中心粒 SDA 分层组装和微管锚定的分子基础。