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

点击翻译按钮获取中文摘要

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