Heat shock induces rapid resorption of primary cilia.
Heat shock induces rapid resorption of primary cilia.
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DOI：
10.1242/jcs.100545
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发表时间：
2012-09-15
影响因子：
4
通讯作者：
Chapple JP
中科院分区：
文献类型：
--
作者：
Prodromou NV;Thompson CL;Osborn DP;Cogger KF;Ashworth R;Knight MM;Beales PL;Chapple JP
初级纤毛参与重要的发育和疾病途径，如神经发生和肿瘤发生的调节。它们作为感觉触角发挥作用，在关键细胞外信号系统的调节中至关重要。我们研究了细胞应激对初级纤毛的影响。体外哺乳动物细胞和体内斑马鱼细胞暴露于升高的温度导致纤毛通过再吸收迅速丧失。在哺乳动物细胞中，纤毛的丧失与刺猬信号的减少有关。热休克依赖性损失的纤毛减少组蛋白去乙酰化酶（HDAC）被抑制的细胞，这表明再吸收介导的轴突定位微管蛋白去乙酰化酶HDAC6。在耐热细胞的纤毛吸收率降低。这意味着分子伴侣在维持初级纤毛中的作用。胞质伴侣Hsp90定位于纤毛轴丝，其抑制导致纤毛损失。在未应激细胞的细胞质中，已知Hsp90与HDAC 6以复合物形式存在。此外，热休克后，Hsp90水平立即减少，在其余的纤毛。我们假设纤毛吸收可以减弱纤毛介导的信号通路以响应细胞外应激，并且这种机制部分受到HDAC 6和Hsp90的调节。
Primary cilia are involved in important developmental and disease pathways, such as the regulation of neurogenesis and tumorigenesis. They function as sensory antennae and are essential in the regulation of key extracellular signalling systems. We have investigated the effects of cell stress on primary cilia. Exposure of mammalian cells in vitro, and zebrafish cells in vivo, to elevated temperature resulted in the rapid loss of cilia by resorption. In mammalian cells loss of cilia correlated with a reduction in hedgehog signalling. Heat-shock-dependent loss of cilia was decreased in cells where histone deacetylases (HDACs) were inhibited, suggesting resorption is mediated by the axoneme-localised tubulin deacetylase HDAC6. In thermotolerant cells the rate of ciliary resorption was reduced. This implies a role for molecular chaperones in the maintenance of primary cilia. The cytosolic chaperone Hsp90 localises to the ciliary axoneme and its inhibition resulted in cilia loss. In the cytoplasm of unstressed cells, Hsp90 is known to exist in a complex with HDAC6. Moreover, immediately after heat shock Hsp90 levels were reduced in the remaining cilia. We hypothesise that ciliary resorption serves to attenuate cilia-mediated signalling pathways in response to extracellular stress, and that this mechanism is regulated in part by HDAC6 and Hsp90.
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影响因子：
4
作者：
Seeley, E. Scott;Nachury, Maxence V.
通讯作者：
Nachury, Maxence V.
影响因子：
11.4
作者：
Lange, BMH;Bachi, A;González, C
通讯作者：
González, C
DOI：
10.1002/ajmg.c.30231
发表时间：
2009-11-15
影响因子：
3.1
作者：
Baker, Kate;Beales, Philip L.
通讯作者：
Beales, Philip L.
DOI：
10.1073/pnas.0804558105
发表时间：
2008-09-02
影响因子：
11.1
作者：
Breunig, Joshua J.;Sarkisian, Matthew R.;Town, Terrence
通讯作者：
Town, Terrence
影响因子：
64.8
作者：
Corbit, KC;Aanstad, P;Reiter, JF
通讯作者：
Reiter, JF