Department of Biochemistry & Biophysics, University of California GH-N372F Genentech Hall, Box 2200, UCSF, 600 16th St. San Francisco, CA 94158, USA.
Differentiation. 2012 Feb;83(2):S30-42. doi: 10.1016/j.diff.2011.11.015. Epub 2011 Dec 16.
Cilia and flagella are highly conserved eukaryotic microtubule-based organelles that protrude from the surface of most mammalian cells. These structures require large protein complexes and motors for distal addition of tubulin and extension of the ciliary membrane. In order for ciliogenesis to occur, coordination of many processes must take place. An intricate concert of cell cycle regulation, vesicular trafficking, and ciliary extension must all play out with accurate timing to produce a cilium. Here, we review the stages of ciliogenesis as well as regulation of the length of the assembled cilium. Regulation of ciliogenesis during cell cycle progression centers on centrioles, from which cilia extend upon maturation into basal bodies. Centriole maturation involves a shift from roles in cell division to cilium nucleation via migration to the cell surface and docking at the plasma membrane. Docking is dependent on a variety of proteinaceous structures, termed distal appendages, acquired by the mother centriole. Ciliary elongation by the process of intraflagellar transport (IFT) ensues. Direct modification of ciliary structures, as well as modulation of signal transduction pathways, play a role in maintenance of the cilium. All of these stages are tightly regulated to produce a cilium of the right size at the right time. Finally, we discuss the implications of abnormal ciliogenesis and ciliary length control in human disease as well as some open questions.
纤毛和鞭毛是高度保守的真核细胞微管基细胞器，从大多数哺乳动物细胞表面伸出。这些结构需要大型蛋白质复合物和马达来进行远端添加微管和纤毛膜的延伸。为了发生纤毛发生，必须协调许多过程。细胞周期调控、囊泡运输和纤毛延伸的复杂协调必须以准确的时间进行，以产生纤毛。在这里，我们回顾纤毛发生的阶段以及组装纤毛长度的调节。细胞周期进程中纤毛发生的调节集中在中心体上，纤毛从成熟的中心体延伸到基底体。中心体成熟涉及从细胞分裂角色向纤毛发生的转变，通过迁移到细胞表面并在质膜上对接。对接取决于通过母亲中心体获得的各种蛋白结构，称为远端附属物。纤毛通过鞭毛内运输（IFT）的过程伸长。对纤毛结构的直接修饰以及信号转导途径的调节在纤毛维持中起作用。所有这些阶段都受到严格调节，以在正确的时间产生正确大小的纤毛。最后，我们讨论了人类疾病中异常纤毛发生和纤毛长度控制的意义以及一些悬而未决的问题。
