The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 15 Nov 2005
doi: 10.1242/jcs.02665
Research Article
The C. elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception
Marlene E. Winkelbauer,
Jenny C. Schafer,
Courtney J. Haycraft,
Peter Swoboda,
and
Bradley K. Yoder*
* Author for correspondence (e-mail: Byoder{at}uab.edu)
Nephronophthisis (NPH) is a cystic kidney disorder that causes end-stage renal failure in children. Five nephrocystin (nephrocystin-1 to nephrocystin-5) genes, whose function is disrupted in NPH patients, have been identified and data indicate they form a complex at cell junctions and focal adhesions. More recently, the nephrocystin proteins have also been identified in cilia, as have multiple other cystic kidney disease related proteins. Significant insights into this cilia and cystic kidney disease connection have come from analyses in simpler eukaryotic organisms such as Caenorhabditis elegans. In this regard, we became interested in the C. elegans homologs of nephrocystin-1 (nph-1) and nephrocystin-4 (nph-4) from a database screen to identify genes coordinately regulated by the ciliogenic transcription factor DAF-19. Here we show that expression of nph-1 and nph-4 is DAF-19 dependent, that their expression is restricted to ciliated sensory neurons, and that both NPH-1 and NPH-4 concentrate at the transition zones at the base of the cilia, but are not found in the cilium axoneme. In addition, NPH-4 is required for the localization of NPH-1 to this domain. Interestingly, nph-1 or nph-4 mutants have no obvious cilia assembly defects; however, they do have abnormalities in cilia-mediated sensory functions as evidenced by abnormal chemotaxis and lifespan regulation. Our data suggest that rather than having a ciliogenic role, the NPH proteins play an important function as part of the sensory or signaling machinery of this organelle. These findings suggest that the defects in human NPH patients may not be the result of aberrant ciliogenesis but abnormal cilia-sensory functions.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Dammermann, H. Pemble, B. J. Mitchell, I. McLeod, J. R. Yates III, C. Kintner, A. B. Desai, and K. Oegema
The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation
Genes & Dev.,
September 1, 2009;
23(17):
2046 - 2059.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. J. Bialas, P. N. Inglis, C. Li, J. F. Robinson, J. D. K. Parker, M. P. Healey, E. E. Davis, C. D. Inglis, T. Toivonen, D. C. Cottell, et al.
Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins
J. Cell Sci.,
March 1, 2009;
122(5):
611 - 624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Hildebrandt, M. Attanasio, and E. Otto
Nephronophthisis: Disease Mechanisms of a Ciliopathy
J. Am. Soc. Nephrol.,
January 1, 2009;
20(1):
23 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Williams, M. E. Winkelbauer, J. C. Schafer, E. J. Michaud, and B. K. Yoder
Functional Redundancy of the B9 Proteins and Nephrocystins in Caenorhabditis elegans Ciliogenesis
Mol. Biol. Cell,
May 1, 2008;
19(5):
2154 - 2168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. D. Smith, M. Tsuchiya, L. A. Fox, N. Dang, D. Hu, E. O. Kerr, E. D. Johnston, B. N. Tchao, D. N. Pak, K. L. Welton, et al.
Quantitative evidence for conserved longevity pathways between divergent eukaryotic species
Genome Res.,
April 1, 2008;
18(4):
564 - 570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Jauregui, K. C.Q. Nguyen, D. H. Hall, and M. M. Barr
The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure
J. Cell Biol.,
March 5, 2008;
180(5):
973 - 988.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. McEwen, R. K. Koenekoop, H. Khanna, P. M. Jenkins, I. Lopez, A. Swaroop, and J. R. Martens
Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons
PNAS,
October 2, 2007;
104(40):
15917 - 15922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Hildebrandt and W. Zhou
Nephronophthisis-Associated Ciliopathies
J. Am. Soc. Nephrol.,
June 1, 2007;
18(6):
1855 - 1871.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. Yoder
Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease
J. Am. Soc. Nephrol.,
May 1, 2007;
18(5):
1381 - 1388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W. Bisgrove and H. J. Yost
The roles of cilia in developmental disorders and disease
Development,
November 1, 2006;
133(21):
4131 - 4143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Schafer, M. E. Winkelbauer, C. L. Williams, C. J. Haycraft, R. A. Desmond, and B. K. Yoder
IFTA-2 is a conserved cilia protein involved in pathways regulating longevity and dauer formation in Caenorhabditis elegans
J. Cell Sci.,
October 1, 2006;
119(19):
4088 - 4100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Fliegauf, J. Horvath, C. von Schnakenburg, H. Olbrich, D. Muller, J. Thumfart, B. Schermer, G. J. Pazour, H. P.H. Neumann, H. Zentgraf, et al.
Nephrocystin Specifically Localizes to the Transition Zone of Renal and Respiratory Cilia and Photoreceptor Connecting Cilia
J. Am. Soc. Nephrol.,
September 1, 2006;
17(9):
2424 - 2433.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2005
