期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 85, 期 6, 页码 883-889出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2009.10.018
关键词
-
资金
- Deutsche Forschungsgemeinschaft (DFG) [Om 6/4, GRK1104, SF13592]
- U.S. National Heart, Lung and Blood Institute and the National Institutes of Health (NIH) [GCRC 00046, R01 HL071798]
- U.S. National Center for Research Resources and the NIH [5 U54 RR019480]
Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility in primary ciliary dyskinesia (PCD). The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Here, we demonstrate that large genomic deletions, as well as point mutations involving LRRC50, are responsible for a distinct PCD variant that is characterized by a combined defect involving assembly of the ODAs and IDAs. Functional analyses showed that LRRC50 deficiency disrupts assembly of distally and proximally DNAHS- and DNA12-containing ODA complexes, as well as DNALI1-containing IDA complexes, resulting in immotile cilia. On the basis of these findings, we assume that LRRC50 plays a role in assembly of distinct dynein-arm complexes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据