Soluble levels of cytosolic tubulin regulate ciliary length control.
Soluble levels of cytosolic tubulin regulate ciliary length control.
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DOI：
10.1091/mbc.e10-03-0269
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发表时间：
2011-03-15
影响因子：
3.3
通讯作者：
Yoder BK
中科院分区：
文献类型：
--
作者：
Sharma N;Kosan ZA;Stallworth JE;Berbari NF;Yoder BK
我们发现操纵微管或肌动蛋白细胞骨架对纤毛长度控制有意想不到的影响。初级纤毛是一个进化上保守的动态细胞器，对调节许多信号通路很重要，因此，破坏纤毛发生的突变会导致各种发育异常和产后疾病。纤毛的长度是由细胞通过未知的机制来调节的。正常纤毛长度很重要，因为纤毛缩短或拉长都与疾病和发育缺陷有关。在这里，我们探讨了细胞骨架动力学在调节纤毛长度中的重要性。利用不同细胞类型的药理学方法，我们证明了肌动蛋白解聚或稳定和蛋白激酶A激活导致初级纤毛的快速伸长。药理学药物对纤毛长度的影响与随后可溶性微管蛋白水平的增加有关，并可通过用紫杉醇消耗可溶性微管蛋白而受损。此外，微妙的诺可达唑处理能够在纤毛不正常形成的条件下诱导纤毛发生，并增加已经建立纤毛的细胞上的纤毛长度。综上所述，这些数据表明纤毛长度可以通过肌动蛋白或微管网络的变化来调节，并暗示可溶性微管蛋白水平在纤毛长度控制中的可能作用。
We show that manipulation of either the microtubule or the actin cytoskeleton has unexpected influences on cilia length control. The primary cilium is an evolutionarily conserved dynamic organelle important for regulating numerous signaling pathways, and, as such, mutations disrupting ciliogenesis result in a variety of developmental abnormalities and postnatal disorders. The length of the cilium is regulated by the cell through largely unknown mechanisms. Normal cilia length is important, as either shortened or elongated cilia have been associated with disease and developmental defects. Here we explore the importance of cytoskeletal dynamics in regulating cilia length. Using pharmacological approaches in different cell types, we demonstrate that actin depolymerization or stabilization and protein kinase A activation result in a rapid elongation of the primary cilium. The effects of pharmacological agents on cilia length are associated with a subsequent increase in soluble tubulin levels and can be impaired by depletion of soluble tubulin with taxol. In addition, subtle nocodazole treatment was able to induce ciliogenesis under conditions in which cilia are not normally formed and also increases cilia length on cells that have already established cilia. Together these data indicate that cilia length can be regulated through changes in either the actin or microtubule network and implicate a possible role for soluble tubulin levels in cilia length control.