help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on April 21, 2005, doi:10.1165/rcmb.2004-0335OC

Am. J. Respir. Cell Mol. Biol., Volume 33, Number 1, July 2005, 41-47

A more recent version of this article appeared on July 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2004-0335OCv1
33/1/41    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Horvath, J.
Right arrow Articles by Omran, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Horvath, J.
Right arrow Articles by Omran, H.

Submitted on October 28, 2004
Revised on April 15, 2005

Identification and Analysis of Axonemal Dynein Light Chain 1 in Primary Ciliary Dyskinesia Patients

Judit Horvath1, Manfred Fliegauf1, Heike Olbrich1, Andreas Kispert2, Stephen M King3, Hannah Mitchison4, Maimoona A Zariwala5, Michael R Knowles5, Ralf Sudbrak6, Gyorgy Fekete7, Juergen Neesen8, Richard Reinhardt6, and Heymut Omran1*

1 Department of Pediatrics and Adolescent Medicine, Albert-Ludwigs-University, Freiburg, Germany, 2 Institut fur Molekularbiologie, Medizinische Hochschule, Hannover, Germany, 3 Department of Biochemistry, University of Connecticut Health Center, Farmington CT, USA, 4 Department of Paediatrics and Child Health, Royal Free and University College Medical School, London, United Kingdom, 5 Department of Medicine, University of North Carolina, Chapel Hill, USA, 6 Max-Planck Institut for Molecular Genetics, Berlin, Germany, 7 Second Department of Pediatrics, School of Medicine, Semmelweis University, Budapest, Hungary, 8 Institute of Human Genetics, University of Goettingen, Goettingen, Germany

* To whom correspondence should be addressed. E-mail: omran{at}kikli.ukl.uni-freiburg.de.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by chronic infections of the upper and lower airways, randomization of left/right body asymmetry and reduced fertility. The phenotype results from dysfunction of motile cilia of the respiratory epithelium, at the embryonic node and of sperm flagella. Ultrastructural defects often involve outer dynein arms (ODAs), that are composed of several light (LCs), intermediate and heavy (HCs) dynein chains. We recently showed that recessive mutations of DNAH5, the human ortholog of the biflagellate Chlamydomonas ODA {gamma}-HC, cause PCD. In Chlamydomonas motor protein activity of the {gamma}-ODA-HC is regulated by binding of the axonemal LC1. We report the identification of the human (DNAL1) and murine (Dnal1) orthologs of the Chlamydomonas LC1-gene. Northern blot and in situ hybridization analyses revealed specific expression in testis, embryonic node, respiratory epithelium and ependyma, resembling the DNAH5 expression pattern. In silico protein analysis showed complete conservation of the LC1/{gamma}-HC binding motif in DNAL1. Protein interaction studies demonstrated binding of DNAL1 and DNAH5. Based on these findings we considered DNAL1 a candidate for PCD and sequenced all exons of DNAL1 in 86 patients. Mutational analysis was negative, excluding a major role of DNAL1 in the pathogenesis of PCD.




This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
D. M. Baron, Z. P. Kabututu, and K. L. Hill
Stuck in reverse: loss of LC1 in Trypanosoma brucei disrupts outer dynein arms and leads to reverse flagellar beat and backward movement
J. Cell Sci., May 1, 2007; 120(9): 1513 - 1520.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. Duriez, P. Duquesnoy, E. Escudier, A.-M. Bridoux, D. Escalier, I. Rayet, E. Marcos, A.-M. Vojtek, J.-F. Bercher, and S. Amselem
A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia
PNAS, February 27, 2007; 104(9): 3336 - 3341.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society. 		  CCM abstracts