Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis.
Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis.
复制标题
DOI：
10.1038/ncomms5207
复制
发表时间：
2014-06-20
影响因子：
16.6
通讯作者：
Swaroop, Anand
中科院分区：
文献类型：
--
作者：
Veleri, Shobi;Manjunath, Souparnika H.;Fariss, Robert N.;May-Simera, Helen;Brooks, Matthew;Foskett, Trevor A.;Gao, Chun;Longo, Teresa A.;Liu, Pinghu;Nagashima, Kunio;Rachel, Rivka A.;Li, Tiansen;Dong, Lijin;Swaroop, Anand
初级纤毛起源于母体中心粒，并在器官发生过程中参与重要功能。纤毛生物发生或功能的缺陷导致多效性表型。中心体纤毛基因CC 2D 2A突变导致Meckel和Joubert综合征。在这里，我们产生了Cc 2d 2a-/-小鼠，其概括了Meckel综合征的特征，包括胚胎致死性和多器官缺陷。纤毛是不存在的Cc 2d 2a-/-胚胎节点和其他体细胞组织;纤毛依赖的Shh信号中断似乎是暴露在突变体胚胎。Cc 2d 2a-/-小鼠胚胎成纤维细胞（MEFs）缺乏纤毛，但检测到母亲中心粒和中心粒周蛋白。Odf 2，与近远侧附属物，是缺席和ninein减少突变MEFs。在Cc 2d 2a-/- MEFs中，近远侧附件缺乏或异常。与此一致，CC 2D 2A通过免疫EM在野生型细胞中定位于近远侧附属物。我们的结论是，CC 2D 2A是必不可少的近远侧附属物，其中锚细胞质微管和总理的母亲中心粒轴丝生物发生的组装。
The primary cilium originates from the mother centriole and participates in critical functions during organogenesis. Defects in cilia biogenesis or function lead to pleiotropic phenotypes. Mutations in centrosome-cilia gene CC2D2A result in Meckel and Joubert syndromes. Here we generate a Cc2d2a-/- mouse that recapitulates features of Meckel syndrome including embryonic lethality and multi-organ defects. Cilia are absent in Cc2d2a-/- embryonic node and other somatic tissues; disruption of cilia-dependent Shh signaling appears to underlie exencephaly in mutant embryos. The Cc2d2a-/- mouse embryonic fibroblasts (MEFs) lack cilia though mother centriole and pericentriolar proteins are detected. Odf2, associated with subdistal appendages, is absent and ninein is reduced in mutant MEFs. In Cc2d2a-/- MEFs, subdistal appendages are lacking or abnormal by transmission-EM. Consistent with this, CC2D2A localizes to subdistal appendages by immuno-EM in wild type cells. We conclude that CC2D2A is essential for the assembly of subdistal appendages, which anchor cytoplasmic microtubules and prime the mother centriole for axoneme biogenesis.
登录
查看更多内容
DOI：
10.4161/cc.24330
发表时间：
2013-04-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Hehnly H;Hung HF;Doxsey S
通讯作者：
Doxsey S
影响因子：
9.8
作者：
Gorden, Nicholas T.;Arts, Heleen H.;Doherty, Dan
通讯作者：
Doherty, Dan
影响因子：
3.3
作者：
Guarguaglini, G;Duncan, PI;Nigg, EA
通讯作者：
Nigg, EA
DOI：
10.1083/jcb.201006105
发表时间：
2010-09-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Craige B;Tsao CC;Diener DR;Hou Y;Lechtreck KF;Rosenbaum JL;Witman GB
通讯作者：
Witman GB
影响因子：
7.5
作者：
Bornens, M
通讯作者：
Bornens, M