Miyoshi Ko, Kasahara Kyosuke, Miyazaki Ikuko, Asanuma Masato
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Acta Med Okayama. 2011 Oct;65(5):279-85. doi: 10.18926/AMO/47009.
Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells;this phenomenon is likely independent of glycogen synthase kinase-3β inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors.
几乎所有哺乳动物细胞都有一根初级纤毛,其作为化学和机械刺激的生物传感器发挥作用。损害纤毛形成或功能的基因损伤会导致一系列被称为纤毛病的疾病。最近的研究表明,一些药物制剂和细胞外环境变化可改变初级纤毛的长度。肾损伤是引发纤毛长度改变的一种已知环境损伤实例。锂处理会使包括神经元细胞在内的多种细胞类型中的初级纤毛伸长;这种现象可能与糖原合酶激酶-3β抑制无关。在肾上皮细胞系中,流体剪切力使初级纤毛发生偏转,通过降低细胞内环磷酸腺苷水平使其缩短,进而导致对流体剪切力的机械敏感性随后降低。初级纤毛的长度还受肌动蛋白丝和微管动力学的影响,这是通过可用于初级纤毛伸长的胞质溶胶中可溶性微管蛋白的水平实现的。因此,哺乳动物细胞可通过调节初级纤毛长度来适应细胞外环境,并且这种利用初级纤毛的反馈系统可能存在于整个哺乳动物体内。关于响应环境因素控制初级纤毛长度的精确分子机制,还需要进一步研究。