Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.

Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina.
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DOI:
10.1016/j.celrep.2016.09.089
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发表时间:
2016-10-25
期刊:
影响因子:
8.8
通讯作者:
Li T
Li T
中科院分区:
生物学1区
文献类型:
--
作者:
May-Simera HL;Gumerson JD;Gao C;Campos M;Cologna SM;Beyer T;Boldt K;Kaya KD;Patel N;Kretschmer F;Kelley MW;Petralia RS;Davey MG;Li T

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微管肌动蛋白交联因子1(Macf 1)在多种细胞过程中微管和肌动蛋白的协调中发挥作用。在这里,我们表明,Macf 1也是在多种细胞类型的纤毛发生的关键。在发育中的视网膜中Macf 1的消融废除了纤毛发生,并且基底体未能停靠到睫状囊泡或向顶部迁移。当视网膜内层细胞正确叠层时,光感受器极性是随机的,这表明光感受器成熟是由纤毛提供的极性线索指导的。Macf 1在成人光感受器中的缺失导致基底体对接的逆转和外节的损失,反映了对Macf 1功能的持续需求。Macf 1还与纤毛蛋白Mkks和Talpid 3相互作用。我们建议,中断跨微管的肌动蛋白丝的运输的基础上缺乏Macf 1的细胞中的纤毛发生缺陷,和Mkks和Talpid 3参与微管和肌动蛋白相互作用的协调。May-Simera等人发现,MACF 1是一种介导微管和肌动蛋白相互作用的巨大蛋白质,对纤毛发生和维持至关重要。在发育中的视网膜中,需要MACF 1来建立光感受器中的顶基底极性,从而突出纤毛在提供正确位置线索中的重要性。
Microtubule actin crosslinking factor 1 (Macf1) plays a role in the coordination of microtubules and actin in multiple cellular processes. Here we show that Macf1 is also critical for ciliogenesis in multiple cell types. Ablation of Macf1 in the developing retina abolishes ciliogenesis, and basal bodies fail to dock to ciliary vesicles or migrate apically. Photoreceptor polarity is randomized while inner retinal cells laminate correctly, suggesting that photoreceptor maturation is guided by polarity cues provided by cilia. Deletion of Macf1 in adult photoreceptors causes reversal of basal body docking and loss of outer segments, reflecting a continuous requirement for Macf1 function. Macf1 also interacts with the ciliary proteins Mkks and Talpid3. We propose that a disruption of trafficking across microtubles to actin filaments underlies the ciliogenesis defect in cells lacking Macf1, and that Mkks and Talpid3 are involved in the coordination of microtubule and actin interactions. May-Simera et al. find that MACF1, a giant protein that mediates microtubule and actin interactions, is essential for ciliogenesis and maintenance. In the developing retina, MACF1 is required for establishing apicobasal polarity in photoreceptors thus highlighting the importance of cilia in providing the correct positional cues.
单克隆抗体揭示的纤毛上皮细胞顶端的肌球蛋白。
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