Abstract
Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease in children and young adults. In Chlamydomonas reinhardtii, Caenorhabditis elegans, and mammals, the NPHP1 and NPHP4 gene products nephrocystin-1 and nephrocystin-4 localize to basal bodies or ciliary transition zones (TZs), but their function in this location remains unknown. We show here that loss of C. elegans NPHP-1 and NPHP-4 from TZs is tolerated in developing cilia but causes changes in localization of specific ciliary components and a broad range of subtle axonemal ultrastructural defects. In amphid channel cilia, nphp-4 mutations cause B tubule defects that further disrupt intraflagellar transport (IFT). We propose that NPHP-1 and NPHP-4 act globally at the TZ to regulate ciliary access of the IFT machinery, axonemal structural components, and signaling molecules, and that perturbing this balance results in cell type-specific phenotypes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 973-988 |
| Number of pages | 16 |
| Journal | Journal of Cell Biology |
| Volume | 180 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 10 2008 |
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ASJC Scopus subject areas
- Cell Biology
Cite this
The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure. / Jauregui, Andrew R.; Nguyen, Ken C.Q.; Hall, David H.; Barr, Maureen M.
In: Journal of Cell Biology, Vol. 180, No. 5, 10.03.2008, p. 973-988.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure
AU - Jauregui, Andrew R.
AU - Nguyen, Ken C.Q.
AU - Hall, David H.
AU - Barr, Maureen M.
PY - 2008/3/10
Y1 - 2008/3/10
N2 - Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease in children and young adults. In Chlamydomonas reinhardtii, Caenorhabditis elegans, and mammals, the NPHP1 and NPHP4 gene products nephrocystin-1 and nephrocystin-4 localize to basal bodies or ciliary transition zones (TZs), but their function in this location remains unknown. We show here that loss of C. elegans NPHP-1 and NPHP-4 from TZs is tolerated in developing cilia but causes changes in localization of specific ciliary components and a broad range of subtle axonemal ultrastructural defects. In amphid channel cilia, nphp-4 mutations cause B tubule defects that further disrupt intraflagellar transport (IFT). We propose that NPHP-1 and NPHP-4 act globally at the TZ to regulate ciliary access of the IFT machinery, axonemal structural components, and signaling molecules, and that perturbing this balance results in cell type-specific phenotypes.
AB - Nephronophthisis (NPHP) is the most common genetic cause of end-stage renal disease in children and young adults. In Chlamydomonas reinhardtii, Caenorhabditis elegans, and mammals, the NPHP1 and NPHP4 gene products nephrocystin-1 and nephrocystin-4 localize to basal bodies or ciliary transition zones (TZs), but their function in this location remains unknown. We show here that loss of C. elegans NPHP-1 and NPHP-4 from TZs is tolerated in developing cilia but causes changes in localization of specific ciliary components and a broad range of subtle axonemal ultrastructural defects. In amphid channel cilia, nphp-4 mutations cause B tubule defects that further disrupt intraflagellar transport (IFT). We propose that NPHP-1 and NPHP-4 act globally at the TZ to regulate ciliary access of the IFT machinery, axonemal structural components, and signaling molecules, and that perturbing this balance results in cell type-specific phenotypes.
UR - http://www.scopus.com/inward/record.url?scp=40849097592&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40849097592&partnerID=8YFLogxK
U2 - 10.1083/jcb.200707090
DO - 10.1083/jcb.200707090
M3 - Article
C2 - 18316409
AN - SCOPUS:40849097592
VL - 180
SP - 973
EP - 988
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 5
ER -