Sentan: A Novel Specific Component of the Apical Structure of Vertebrate Motile Cilia
Sentan: A Novel Specific Component of the Apical Structure of Vertebrate Motile Cilia
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DOI：
10.1091/mbc.e08-07-0691
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发表时间：
2008-12-01
影响因子：
3.3
通讯作者：
Amagai, Masayuki
中科院分区：
文献类型：
--
作者：
Kubo, Akiharu;Yuba-Kubo, Akiko;Amagai, Masayuki
人类呼吸道和输卵管纤毛具有特定的顶端结构，其特征在于狭窄的远端部分和纤毛冠。这些结构在具有空气呼吸系统的脊椎动物中是保守的;然而，这些结构的分子组成尚未被定义，并且它们的功能未知。为了鉴定纤毛顶端结构的分子成分，我们筛选了EST库，以鉴定仅在纤毛组织中表达、在体外纤毛发生过程中转录上调且在睾丸中不表达的基因（因为精子鞭毛）没有这样的顶端结构）。其中一个被鉴定的基因产物被命名为sentan，定位于运动纤毛的远端区域。使用抗sentan多克隆抗体和电子显微镜，sentan被证明专门定位于细胞膜和外周单线态微管之间的桥接结构，其具体存在于纤毛的狭窄远端部分。外源性表达的sentan表现出对膜突起的亲和力，并且蛋白质-脂质结合测定显示sentan与磷脂酰丝氨酸结合。这些发现表明，sentan是纤毛尖端的第一个分子组分，用于桥接细胞膜和外周单线态微管，使纤毛的远端部分变窄和变硬，以允许更好的气道清除或卵子运输。
Human respiratory and oviductal cilia have specific apical structures characterized by a narrowed distal portion and a ciliary crown. These structures are conserved among vertebrates that have air respiration systems; however, the molecular components of these structures have not been defined, and their functions are unknown. To identify the molecular component(s) of the cilia apical structure, we screened EST libraries to identify gene(s) that are exclusively expressed in ciliated tissues, are transcriptionally up-regulated during in vitro ciliogenesis, and are not expressed in testis (because sperm flagella have no such apical structures). One of the identified gene products, named sentan, was localized to the distal tip region of motile cilia. Using anti-sentan polyclonal antibodies and electron microscopy, sentan was shown to localize exclusively to the bridging structure between the cell membrane and peripheral singlet microtubules, which specifically exists in the narrowed distal portion of cilia. Exogenously expressed sentan showed affinity for the membrane protrusions, and a protein-lipid binding assay revealed that sentan bound to phosphatidylserine. These findings suggest that sentan is the first molecular component of the ciliary tip to bridge the cell membrane and peripheral singlet microtubules, making the distal portion of the cilia narrow and stiff to allow for better airway clearance or ovum transport.