Ciliated sensory hair cell formation and function require the F-BAR protein syndapin I and the WH2 domain-based actin nucleator Cobl
Ciliated sensory hair cell formation and function require the F-BAR protein syndapin I and the WH2 domain-based actin nucleator Cobl
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DOI：
10.1242/jcs.111674
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发表时间：
2013-01
影响因子：
4
通讯作者：
Susann Schüler;Judith Hauptmann;B. Perner;M. Kessels;C. Englert;B. Qualmann
中科院分区：
文献类型：
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作者：
Susann Schüler;Judith Hauptmann;B. Perner;M. Kessels;C. Englert;B. Qualmann
在发育过程中，一般的身体计划信息必须转化为单个细胞的不同形态。塑形细胞被认为涉及皮质细胞骨架成分和Bin-Amphiphysin-Rvs167 （BAR）超家族蛋白。因此，我们对F-BAR蛋白syndapin I和肌动蛋白核子Cobl的斑马鱼同源物进行了全面的并排功能丧失研究。斑马鱼突触蛋白1与Cobl有关。这些蛋白的功能缺失表型非常相似，表明它们具有共同的功能。cobli型和syndapin i型鱼均表现出严重的游泳和平衡缺陷，反映了侧线器官的组织和功能受损。他们的侧线器官缺少几个神经突，神经突内的感觉毛细胞功能受损。扫描电镜显示，cobl-和syndapin - i型动物的感觉毛细胞在微管依赖性纤毛和富含f -actin的立体纤毛的形成上都存在缺陷。与感觉毛细胞的纤毛缺陷一致，体长缩短，依赖于纤毛运动的身体侧边发育也受到损害。有趣的是，Cobl和syndapin I都定位于形成纤毛的基部。修复实验表明，纤毛感觉毛细胞簇的形成依赖于Cobl的syndapin I结合同源结构域、Cobl的肌动蛋白成核c端和syndapin I诱导膜曲率的F-BAR结构域。因此，我们的数据表明，不同类型纤毛结构的形成依赖于基于F-BAR结构域功能的膜拓扑调节机制，以及syndapin I与肌动蛋白成核子Cobl的复杂形成。
Summary During development, general body plan information must be translated into distinct morphologies of individual cells. Shaping cells is thought to involve cortical cytoskeletal components and Bin-Amphiphysin-Rvs167 (BAR) superfamily proteins. We therefore conducted comprehensive side-by-side loss-of-function studies of zebrafish orthologs of the F-BAR protein syndapin I and the actin nucleator Cobl. Zebrafish syndapin I associates with Cobl. The loss-of-function phenotypes of these proteins were remarkably similar and suggested a common function. Both cobl- and syndapin I-morphant fish showed severe swimming and balance-keeping defects, reflecting an impaired organization and function of the lateral line organ. Their lateral line organs lacked several neuromasts and showed an impaired functionality of the sensory hair cells within the neuromasts. Scanning electron microscopy revealed that sensory hair cells of both cobl- and syndapin I-morphant animals showed defects in the formation of both microtubule-dependent kinocilia and F-actin-rich stereocilia. Consistent with the kinocilia defects in sensory hair cells, body length was shortened and the development of body laterality, a process depending on motile cilia, was also impaired. Interestingly, Cobl and syndapin I both localized to the base of forming cilia. Rescue experiments demonstrated that proper formation of ciliated sensory hair cell rosettes relied on Cobl's syndapin I-binding Cobl homology domain, the actin-nucleating C-terminus of Cobl and the membrane curvature-inducing F-BAR domain of syndapin I. Our data thus suggest that the formation of distinct types of ciliary structures relies on membrane topology-modulating mechanisms that are based on F-BAR domain functions and on complex formation of syndapin I with the actin nucleator Cobl.