The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans

被引：150

作者：

Wirschell, Maureen ^{[1
]}

Olbrich, Heike ^{[2
]}

Werner, Claudius ^{[2
]}

Tritschler, Douglas ^{[3
]}

Bower, Raqual ^{[3
]}

Sale, Winfield S. ^{[1
]}

Loges, Niki T. ^{[2
]}

Pennekamp, Petra ^{[2
]}

Lindberg, Sven ^{[4
,5
]}

Stenram, Unne ^{[6
,7
]}

Carlen, Birgitta ^{[6
,7
]}

Horak, Elisabeth ^{[8
]}

Koehler, Gabriele ^{[9
]}

Nuernberg, Peter ^{[10
,11
,12
]}

Nuernberg, Gudrun ^{[10
,11
,12
]}

Porter, Mary E. ^{[3
]}

Omran, Heymut ^{[2
]}

机构：

[1] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA USA

[2] Univ Hosp Muenster, Dept Pediat, Munster, Germany

[3] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA

[4] Lund Univ, Dept Otorhinolaryngol Head & Neck Surg, Lund, Sweden

[5] Skane Univ Hosp SUS, Lund, Sweden

[6] Lund Univ, Dept Pathol, Lund, Sweden

[7] SUS, Lund, Sweden

[8] Med Univ Innsbruck, Div Cardiol & Pulmonol, Dept Pediat & Adolescents, A-6020 Innsbruck, Austria

[9] Univ Hosp Muenster, Inst Pathol, Munster, Germany

[10] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany

[11] Univ Cologne, CMMC, D-50931 Cologne, Germany

[12] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany

来源：

NATURE GENETICS | 2013年 / 45卷 / 03期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

CHLAMYDOMONAS-FLAGELLA; RADIAL SPOKES; DYSKINESIA; INNER; ARMS; MUTATIONS; IDENTIFICATION; ASYMMETRY; DEFECTS; MUTANTS;

D O I：

10.1038/ng.2533

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Primary ciliary dyskinesia (PCD) is characterized by dysfunction of respiratory cilia and sperm flagella and random determination of visceral asymmetry. Here, we identify the DRC1 subunit of the nexin-dynein regulatory complex (N-DRC), an axonemal structure critical for the regulation of dynein motors, and show that mutations in the gene encoding DRC1, CCDC164, are involved in PCD pathogenesis. Loss-of-function mutations disrupting DRC1 result in severe defects in assembly of the N-DRC structure and defective ciliary movement in Chlamydomonas reinhardtii and humans. Our results highlight a role for N-DRC integrity in regulating ciliary beating and provide the first direct evidence that mutations in DRC genes cause human disease.

引用

页码：262 / 268

页数：7

共 31 条

[11] COMPONENTS OF A DYNEIN-REGULATORY-COMPLEX ARE LOCATED AT THE JUNCTION BETWEEN THE RADIAL SPOKES AND THE DYNEIN ARMS IN CHLAMYDOMONAS-FLAGELLA [J].

GARDNER, LC ;

OTOOLE, E ;

PERRONE, CA ;

GIDDINGS, T ;

PORTER, ME .

JOURNAL OF CELL BIOLOGY, 1994, 127 (05) :1311-1325

[12] The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella [J].

Heuser, Thomas ;

Raytchev, Milen ;

Krell, Jeremy ;

Porter, Mary E. ;

Nicastro, Daniela .

JOURNAL OF CELL BIOLOGY, 2009, 187 (06) :921-933

[13] SUPPRESSOR MUTATIONS IN CHLAMYDOMONAS REVEAL A REGULATORY MECHANISM FOR FLAGELLAR FUNCTION [J].

HUANG, B ;

RAMANIS, Z ;

LUCK, DJL .

CELL, 1982, 28 (01) :115-124

[14] CMF70 is a subunit of the dynein regulatory complex [J].

Kabututu, Zakayi P. ;

Thayer, Michelle ;

Melehani, Jason H. ;

Hill, Kent L. .

JOURNAL OF CELL SCIENCE, 2010, 123 (20) :3587-3595

[15] Building Blocks of the Nexin-Dynein Regulatory Complex in Chlamydomonas Flagella [J].

Lin, Jianfeng ;

Tritschler, Douglas ;

Song, Kangkang ;

Barber, Cynthia F. ;

Cobb, Jennifer S. ;

Porter, Mary E. ;

Nicastro, Daniela .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (33) :29175-29191

[16] Diagnostic Value of Nasal Nitric Oxide Measured with Non-Velum Closure Techniques for Children with Primary Ciliary Dyskinesia [J].

Mateos-Corral, Dimas ;

Coombs, Robin ;

Grasemann, Hartmut ;

Ratjen, Felix ;

Dell, Sharon D. .

JOURNAL OF PEDIATRICS, 2011, 159 (03) :420-424

[17] Primary Ciliary Dyskinesia Caused by Homozygous Mutation in DNAL1, Encoding Dynein Light Chain 1 [J].

Mazor, Masha ;

Alkrinawi, Soliman ;

Chalifa-Caspi, Vered ;

Manor, Esther ;

Sheffield, Val C. ;

Aviram, Micha ;

Parvari, Ruti .

AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 88 (05) :599-607

[18] CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs [J].

Merveille, Anne-Christine ;

Davis, Erica E. ;

Becker-Heck, Anita ;

Legendre, Marie ;

Amirav, Israel ;

Bataille, Geraldine ;

Belmont, John ;

Beydon, Nicole ;

Billen, Frederic ;

Clement, Annick ;

Clercx, Cecile ;

Coste, Andre ;

Crosbie, Rachelle ;

de Blic, Jacques ;

Deleuze, Stephane ;

Duquesnoy, Philippe ;

Escalier, Denise ;

Escudier, Estelle ;

Fliegauf, Manfred ;

Horvath, Judith ;

Hill, Kent ;

Jorissen, Mark ;

Just, Jocelyne ;

Kispert, Andreas ;

Lathrop, Mark ;

Loges, Niki Tomas ;

Marthin, June K. ;

Momozawa, Yukihide ;

Montantin, Guy ;

Nielsen, Kim G. ;

Olbrich, Heike ;

Papon, Jean-Francois ;

Rayet, Isabelle ;

Roger, Gilles ;

Schmidts, Miriam ;

Tenreiro, Henrique ;

Towbin, Jeffrey A. ;

Zelenika, Diana ;

Zentgraf, Hanswalter ;

Georges, Michel ;

Lequarre, Anne-Sophie ;

Katsanis, Nicholas ;

Omran, Heymut ;

Amselem, Serge .

NATURE GENETICS, 2011, 43 (01) :72-U98

[19] Computer-assisted image analysis of human cilia and Chlamydomonas flagella reveals both similarities and differences in axoneme structure [J].

O'Toole, Eileen T. ;

Giddings, Thomas H., Jr. ;

Porter, Mary E. ;

Ostrowski, Lawrence E. .

CYTOSKELETON, 2012, 69 (08) :577-590

[20] Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right and asymmetry [J].

Olbrich, H ;

Häffner, K ;

Kispert, A ;

Völkel, A ;

Volz, A ;

Sasmaz, G ;

Reinhardt, R ;

Hennig, S ;

Lehrach, H ;

Konietzko, N ;

Zariwala, M ;

Noone, PG ;

Knowles, M ;

Mitchison, HM ;

Meeks, M ;

Chung, EMK ;

Hildebrandt, F ;

Sudbrak, R ;

Omran, H .

NATURE GENETICS, 2002, 30 (02) :143-144

← 1 2 3 4 →