VDAC3 and Mps1 negatively regulate ciliogenesis
VDAC3 and Mps1 negatively regulate ciliogenesis
复制标题
DOI：
10.4161/cc.23824
复制
发表时间：
2013-03-01
期刊：
影响因子：
4.3
通讯作者：
Fisk, Harold A.
中科院分区：
文献类型：
--
作者：
Majumder, Shubhra;Fisk, Harold A.
在循环细胞中中心体负责组织新的中心粒，而在静止细胞中中心体负责组装初级纤毛。我们最近表明，线粒体孔蛋白VDAC3也是一种中心体蛋白，主要与母中心粒相关，并通过将Mps1招募到中心体来调节中心粒组装。在这里，我们发现VDAC3的缺失导致循环细胞中不适当的纤毛发生，而GFP-VDAC3的表达抑制静止细胞中的纤毛发生。Mps1对纤毛发生也有负调控作用，通过不依赖于VDAC3而将Mps1靶向中心体，可以绕过由VDAC3缺失引起的不适当纤毛发生。因此，我们的数据表明，中心体上的VDAC3-Mps1模块在细胞周期进入时促进纤毛拆卸，并抑制增殖细胞中的纤毛组装。我们的数据还表明，VDAC3可能是哺乳动物细胞中线粒体功能障碍和纤毛病之间的联系。
Centrosomes serve to organize new centrioles in cycling cells, whereas in quiescent cells they assemble primary cilia. We have recently shown that the mitochondrial porin VDAC3 is also a centrosomal protein that is predominantly associated with the mother centriole and modulates centriole assembly by recruiting Mps1 to centrosomes. Here, we show that depletion of VDAC3 causes inappropriate ciliogenesis in cycling cells, while expression of GFP-VDAC3 suppresses ciliogenesis in quiescent cells. Mps1 also negatively regulates ciliogenesis, and the inappropriate ciliogenesis caused by VDAC3 depletion can be bypassed by targeting Mps1 to centrosomes independently of VDAC3. Thus, our data show that a VDAC3-Mps1 module at the centrosome promotes ciliary disassembly during cell cycle entry and suppresses cilia assembly in proliferating cells. Our data also suggests that VDAC3 might be a link between mitochondrial dysfunction and ciliopathies in mammalian cells.