The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure.
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.
Jauregui
Andrew R
AR
Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA.
Nguyen
Ken C Q
KC
Hall
David H
DH
Barr
Maureen M
MM
D000818:Animals; D054468:Axoneme / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D002923:Cilia / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008870:Microtubules / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; C501204:nephrocystin 1, C elegans; C501205:nephrocystin 4, C elegans