ERM proteins as integrators at the cell cortex : Gene knockout study

ERM 蛋白作为细胞皮质的整合者：基因敲除研究

• 批准号: 15370083
• 负责人: TSUKITA Sachiko
• 金额: $ 9.34万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15370083/
• 关键词: actin; ezrin; radixin; moesin; ERM; cytoskeleton; cell adhesion; cell motility; 細胞膜; 情報伝達; 分泌; 膜融合; 細胞接着

Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereociliaWe found that, in cochlear and vestibular sensory hair cells of adult wild-type mice, radixin was specifically enriched in stereocilia, specially-developed giant microvilli, and that radixin-deficient (Rdx^<-/->) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset (〜2 weeks), in the cochlea and vestibule of Rdx^<-/-> mice, stereocilia developed normally in which ezrin was concentrated instead of radixin. As these Rdx^<-/-> mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx^<-/-> mice. We thus concluded that radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once-developed.Achlorhydria by ezrin knockdown : defects in the formation/expansion of apical canaliculi in gastri … More c parietal cellsLoss of gastric acid secretion is pathologically known as achlorhydria. Acid-secreting parietal cells are characterized by abundant expression of ezrin (Vil2), one of ERM (ezrin/radixin/moesin) proteins, which generally cross-link actin filaments with plasma membrane proteins. Here we show the direct in vivo involvement of ezrin in gastric acid secretion. Ezrin-knockout (Vil2^<-/->) mice did not survive more than one week after birth, making difficult to examine gastric acid secretion. We then generated ezrin-knockdown (Vil2^<kd/kd>) mice by introducing a neomycin resistance cassette between exons 2 and 3. Vil2^<kd/kd> mice born at the expected Mendelian ratio exhibited growth retardation and a high mortality. 〜7% of Vil2^<kd/kd> mice survived to adulthood. Ezrin protein levels in Vil2^<kd/kd> stomachs decreased to <5% of the wild-type levels without compensatory up-regulation of radixin or moesin. Adult Vil2^<kd/kd> mice suffered from severe achlorhydria. Immunofluorescence and electron microscopy revealed that this achlorhydria was caused by defects in the formation/expansion of canalicular apical membranes in gastric parietal cells. Less

我们发现，在成年野生型小鼠的耳蜗和前庭感觉毛细胞中，Radixin特异性地富集在静纤毛中，静纤毛是特别发育的巨大微绒毛，并且Radixin缺陷（Rdx^-/->）成年小鼠表现出耳聋，但没有明显的前庭功能障碍。在听力开始的年龄之前（约2周），在Rdx^<-/->小鼠的耳蜗和前庭中，静纤毛正常发育，其中ezrin而不是radixin集中。随着这些Rdx^<-/->小鼠的生长，基于ezrin的耳蜗静纤毛逐渐退化，导致耳聋，而基于ezrin的前庭静纤毛在成年Rdx^<-/->小鼠中保持正常。因此，我们得出结论，radixin是必不可少的小鼠听力，通过维持耳蜗静纤毛，一旦开发。Achloroptera通过ezrin敲低：缺陷的形成/扩大顶端小管在胃肠道 ...更多信息 c壁细胞胃酸分泌的丧失在病理学上被称为胃酸缺乏。分泌酸的壁细胞的特征在于Ezrin（Vil 2）的丰富表达，Ezrin（Vil 2）是ERM（ezrin/radixin/moesin）蛋白之一，其通常将肌动蛋白丝与质膜蛋白交联。在这里，我们显示直接在体内参与埃兹林在胃酸分泌。Ezrin敲除（Vil 2 ^<-/->）小鼠在出生后存活不超过一周，使得难以检查胃酸分泌。然后，我们通过在外显子2和3之间引入新霉素抗性盒来产生ezrin敲低（Vil 2 ^<kd/kd>）小鼠。以预期的孟德尔比率出生的Vil 2 ^<kd/kd>小鼠表现出生长迟缓和高死亡率。约7%的V12 ^<kd/kd>小鼠存活至成年。Vil 2 ^<kd/kd>胃中的Ezrin蛋白水平降低至野生型水平的<5%，而没有根蛋白或膜突蛋白的补偿性上调。成年V12 ^<kd/kd>小鼠患有严重的缺氯症。免疫荧光和电子显微镜显示，这achloroprotea是由缺陷的形成/扩张的小管顶膜在胃壁细胞。少

项目成果

Hamada, K., et al.: "Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM complex"EMBO Journal. 22. 502-514 (2003)

Hamada, K. 等人：“根素-ICAM 复合物的晶体结构揭示了 ERM 蛋白粘附分子识别的结构基础”EMBO 杂志。

Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereocilia.

根黄素缺乏会导致与耳蜗静纤毛进行性退化相关的耳聋。

• DOI: 10.1083/jcb.200402007
• 发表时间: 2004-08-16
• 期刊: The Journal of cell biology
• 作者: Kitajiri S;Fukumoto K;Hata M;Sasaki H;Katsuno T;Nakagawa T;Ito J;Tsukita S;Tsukita S
• 通讯作者: Tsukita S

Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex

• DOI: 10.1093/emboj/cdg039
• 发表时间: 2003-02-03
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Hamada, K;Shimizu, T;Hakoshima, T
• 通讯作者: Hakoshima, T

Achlorhydria by ezrin knockdown: defects in the formation/expansion of apical canaliculi in gastric parietal cells.

• DOI: 10.1083/jcb.200410083
• 发表时间: 2005-04-11
• 期刊: The Journal of cell biology
• 作者: Tamura A;Kikuchi S;Hata M;Katsuno T;Matsui T;Hayashi H;Suzuki Y;Noda T;Tsukita S;Tsukita S
• 通讯作者: Tsukita S

Insights into a single rod-like heliz in activated radixin required for membrane-cytoskeletal cross-linking

深入了解膜-细胞骨架交联所需的活化根素中的单杆状螺旋

• 发表时间: 2003
• 期刊: Biochemistry 42
• 作者: Hoeflich;K.P.;et al.
• 通讯作者: et al.