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The ciliary transition zone functions in cell adhesion but is dispensable for axoneme assembly in C. elegans.

Schouteden C, Serwas D, Palfy M, Dammermann A - J. Cell Biol. (2015)

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria.

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Molecular architecture of the transition zone and function in cell adhesion. (A) 3D reconstruction model of the transition zone in C. elegans, highlighting key features. See also Video 2. Based on protein localization and mutant phenotypes, CCEP-290 is an essential component of the central cylinder (this study), whereas MKS and NPHP module components function in assembly of Y-links (Williams et al., 2011). Transition zone mutants display no apparent defects in axoneme assembly. However, ciliary gating and cell adhesion are compromised. (B) The dendrite of C. elegans amphid and phasmid neurons forms by retrograde extension, with the cell body moving backward while the dendritic tip remains in place. The transition zone mediates tip anchorage via interactions with the extracellular matrix. (C) Positioning of the primary cilium determines cell fate in vertebrate neuroepithelium. Cells with apically positioned cilia maintain their position at the apical adherens junction belt, whereas cells with basolateral cilia delaminate (Wilsch-Bräuninger et al., 2012; Paridaen et al., 2013). Differential signaling, but also mechanical anchorage by the cilium, could explain this result.
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fig4: Molecular architecture of the transition zone and function in cell adhesion. (A) 3D reconstruction model of the transition zone in C. elegans, highlighting key features. See also Video 2. Based on protein localization and mutant phenotypes, CCEP-290 is an essential component of the central cylinder (this study), whereas MKS and NPHP module components function in assembly of Y-links (Williams et al., 2011). Transition zone mutants display no apparent defects in axoneme assembly. However, ciliary gating and cell adhesion are compromised. (B) The dendrite of C. elegans amphid and phasmid neurons forms by retrograde extension, with the cell body moving backward while the dendritic tip remains in place. The transition zone mediates tip anchorage via interactions with the extracellular matrix. (C) Positioning of the primary cilium determines cell fate in vertebrate neuroepithelium. Cells with apically positioned cilia maintain their position at the apical adherens junction belt, whereas cells with basolateral cilia delaminate (Wilsch-Bräuninger et al., 2012; Paridaen et al., 2013). Differential signaling, but also mechanical anchorage by the cilium, could explain this result.

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.


The ciliary transition zone functions in cell adhesion but is dispensable for axoneme assembly in C. elegans.

Schouteden C, Serwas D, Palfy M, Dammermann A - J. Cell Biol. (2015)

Molecular architecture of the transition zone and function in cell adhesion. (A) 3D reconstruction model of the transition zone in C. elegans, highlighting key features. See also Video 2. Based on protein localization and mutant phenotypes, CCEP-290 is an essential component of the central cylinder (this study), whereas MKS and NPHP module components function in assembly of Y-links (Williams et al., 2011). Transition zone mutants display no apparent defects in axoneme assembly. However, ciliary gating and cell adhesion are compromised. (B) The dendrite of C. elegans amphid and phasmid neurons forms by retrograde extension, with the cell body moving backward while the dendritic tip remains in place. The transition zone mediates tip anchorage via interactions with the extracellular matrix. (C) Positioning of the primary cilium determines cell fate in vertebrate neuroepithelium. Cells with apically positioned cilia maintain their position at the apical adherens junction belt, whereas cells with basolateral cilia delaminate (Wilsch-Bräuninger et al., 2012; Paridaen et al., 2013). Differential signaling, but also mechanical anchorage by the cilium, could explain this result.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4493997&req=5

fig4: Molecular architecture of the transition zone and function in cell adhesion. (A) 3D reconstruction model of the transition zone in C. elegans, highlighting key features. See also Video 2. Based on protein localization and mutant phenotypes, CCEP-290 is an essential component of the central cylinder (this study), whereas MKS and NPHP module components function in assembly of Y-links (Williams et al., 2011). Transition zone mutants display no apparent defects in axoneme assembly. However, ciliary gating and cell adhesion are compromised. (B) The dendrite of C. elegans amphid and phasmid neurons forms by retrograde extension, with the cell body moving backward while the dendritic tip remains in place. The transition zone mediates tip anchorage via interactions with the extracellular matrix. (C) Positioning of the primary cilium determines cell fate in vertebrate neuroepithelium. Cells with apically positioned cilia maintain their position at the apical adherens junction belt, whereas cells with basolateral cilia delaminate (Wilsch-Bräuninger et al., 2012; Paridaen et al., 2013). Differential signaling, but also mechanical anchorage by the cilium, could explain this result.
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.

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria.

Show MeSH
Related in: MedlinePlus