期刊
NATURE GENETICS
卷 44, 期 2, 页码 193-199出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.1078
关键词
-
资金
- Marshfield Clinic Research Foundation
- US National Institutes of Health
- National Heart, Lung, and Blood Institute
- US National Institutes of Health [R01NS048453, R01NS052455, R01DK068306, R01NS064077]
- American Heart Association [09POST2250641]
- Italian Ministry of Health
- Telethon Foundation Italy [GGP08145]
- Pierfranco and Luisa Mariani Foundation
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Japan Society for the Promotion of Science (JSPS) [23117517, 23570209]
- Newlife Charity
- Medical Research Council [G0700073]
- Sir Jules Thorn Charitable Trust [09/JTA]
- I'Agence National pour la Recherche (ANR) [07-MRAR]
- Simons Foundation Autism Research Initiative
- Howard Hughes Medical Institute
- MRC [G0700073] Funding Source: UKRI
- Medical Research Council [G0700073] Funding Source: researchfish
- The Sir Jules Thorn Charitable Trust [09JTA] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [23570209] Funding Source: KAKEN
Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function(1,2). However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (IBTS)(3), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein(4). We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase enzyme(5). Depletion of CEP41 causes ciliopathy-related phenotypes in zebrafish and mice and results in glutamylation defects in the ciliary axoneme. Our data identify CEP41 mutations as a cause of JBTS and implicate tubulin post-translational modification in the pathogenesis of human ciliary dysfunction.
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