The ciliary transition zone functions in cell adhesion but is dispensable for axoneme assembly in C. elegans.
Bottom Line: Previous work in Caenorhabditis elegans identified two ciliopathy-associated protein complexes or modules that direct assembly of transition zone Y-links.Co-inhibition of all three modules completely disrupted transition zone structure.Surprisingly, axoneme assembly was only mildly perturbed.
Affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria.Show MeSH
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Mentions: Examination of the C. elegans transition zone by serial-section electron microscopy reveals two prominent ultrastructural features: Y-links connecting axonemal microtubules to the ciliary membrane and the central cylinder to which axonemal outer doublet and inner singlet microtubules are attached (Fig. 1 G; Perkins et al., 1986). Tomographic reconstructions show both structures to be contiguous along the longitudinal axis of the transition zone, forming elongated sheets (Video 2; see also Fig. 4 A). Previous work in C. elegans had implicated MKS and NPHP proteins in assembly of Y-links. Loss of these connectors results in detachment and dilation of the ciliary membrane, while leaving the central cylinder and associated axonemal microtubules intact (Williams et al., 2011). The same role had been ascribed to CEP290 in Chlamydomonas reinhardtii, although Y-links were still observed, albeit rarely, in cep290 mutants (Craige et al., 2010). In contrast, loss of CCEP-290 in C. elegans ccep-290Δ mutants resulted in fragmentation of the central cylinder, disrupting the radially symmetric array of axonemal microtubules (Fig. 1 G). Unlike in MKS/NPHP mutants, there was no detachment of the ciliary membrane and Y-links could still be found in some sections (arrowheads). ccep-290Δ;nphp-4 mutants displayed an intermediate phenotype, with 5/11 transition zones appearing fragmented and the remainder fully disorganized. Finally, disruption of all three modules in ccep-290;mksr-2;nphp-4 triple mutants resulted in a complete loss of transition zone structures, with axonemal microtubule doublets dissociated from each other and the ciliary membrane (Fig. 1 G). These results are consistent with our high-resolution localization data and highlight the distinct roles of CCEP-290 and MKS/NPHP proteins at the transition zone, with CCEP-290 serving as a core component of the central cylinder, which appears to act as an inner scaffold for transition zone assembly, while MKS/NPHP proteins function in assembly of peripheral Y-links.
Affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria.