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

Radixin缺乏症引起耳蜗立体纤毛进行性退行性变耳聋。我们发现，在成年野生型小鼠耳蜗和前庭感觉毛细胞中，Radixin在立体纤毛中特异性富集，特别发育的巨大微绒毛，Radixin缺乏症（Rdx^<-/->）成年小鼠表现为耳聋，但没有明显的前庭功能障碍。在听力发生前（~ 2周），Rdx^<-/->小鼠耳蜗和前庭发育正常，其中集中的是ezrin而不是放射素。随着Rdx^<-/->小鼠的生长，以ezrin为基础的耳蜗立体纤毛逐渐退化，导致耳聋，而在成年Rdx^<-/->小鼠中，以ezrin为基础的前庭立体纤毛保持正常。我们由此得出结论，通过维持小鼠耳蜗立体纤毛，雷根素对小鼠的听力能力是不可或缺的。胃酸分泌减少在病理上被称为胃酸分泌不足。分泌酸壁细胞的特点是大量表达ezrin (Vil2)，这是ERM （ezrin/radixin/moesin）蛋白中的一种，它通常与肌动蛋白丝交联。在这里，我们展示了ezrin在体内直接参与胃酸分泌。ezrin基因敲除（Vil2^<-/->）小鼠在出生后存活不超过一周，因此难以检测胃酸分泌。然后，我们通过在外显子2和3之间引入新霉素抗性盒，产生了ezrin敲低（Vil2^<kd/kd>）的小鼠。Vil2^<kd/kd>按预期孟德尔比率出生的小鼠表现出生长迟缓和高死亡率。~ 7%的Vil2^<kd/kd>小鼠存活至成年。在Vil2^<kd/kd>胃中，Ezrin蛋白水平降至野生型的5%以下，radixin或moesin均未代偿上调。成年小鼠Vil2^<kd/kd>严重缺氯。免疫荧光和电镜显示，胃壁细胞小管尖膜形成/扩张缺陷引起胃壁酸液缺失。少

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