Dataset Information

Cell type-specific structural plasticity of the ciliary transition zone in C. elegans.

ABSTRACT: BACKGROUND INFORMATION:The current consensus on cilia development posits that the ciliary transition zone (TZ) is formed via extension of nine centrosomal microtubules. In this model, TZ structure remains unchanged in microtubule number throughout the cilium life cycle. This model does not however explain structural variations of TZ structure seen in nature and could also lend itself to the misinterpretation that deviations from nine-doublet microtubule ultrastructure represent an abnormal phenotype. Thus, a better understanding of events that occur at the TZ in vivo during metazoan development is required. RESULTS:To address this issue, we characterized ultrastructure of two types of sensory cilia in developing Caenorhabditis elegans. We discovered that, in cephalic male (CEM) and inner labial quadrant (IL2Q) sensory neurons, ciliary TZs are structurally plastic and remodel from one structure to another during animal development. The number of microtubule doublets forming the TZ can be increased or decreased over time, depending on cilia type. Both cases result in structural TZ intermediates different from TZ in cilia of adult animals. In CEM cilia, axonemal extension and maturation occurs concurrently with TZ structural maturation. CONCLUSIONS AND SIGNIFICANCE:Our work extends the current model to include the structural plasticity of metazoan transition zone, which can be structurally delayed, maintained or remodelled in cell type-specific manner.

SUBMITTER: Akella JS

PROVIDER: S-EPMC6922583 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Cell type-specific structural plasticity of the ciliary transition zone in C. elegans.

Akella Jyothi S JS Silva Malan M Morsci Natalia S NS Nguyen Ken C KC Rice William J WJ Hall David H DH Barr Maureen M MM

Biology of the cell 20190214 4

<h4>Background information</h4>The current consensus on cilia development posits that the ciliary transition zone (TZ) is formed via extension of nine centrosomal microtubules. In this model, TZ structure remains unchanged in microtubule number throughout the cilium life cycle. This model does not however explain structural variations of TZ structure seen in nature and could also lend itself to the misinterpretation that deviations from nine-doublet microtubule ultrastructure represent an abnorm ...[more]

PMID: 30681171

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Project description:Cilia have a unique diffusion barrier ("gate") within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease are not completely understood. Here, we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation. Consistent with a critical role in ciliary gate function, CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and keeps ARL-13 (Arl13b) from leaking out of cilia via the TZ. We identify a novel MKS module component, TMEM-218 (Tmem218), that requires CEP-290 and other MKS module components for TZ localisation and functions together with the NPHP module to facilitate ciliogenesis. We show that TZ localisation of TMEM-138 (Tmem138) and CDKL-1 (Cdkl1/Cdkl2/Cdkl3/Cdlk4 related), not previously linked to a specific TZ module, similarly depends on CEP-290; surprisingly, neither TMEM-138 or CDKL-1 exhibit interdependent localisation or genetic interactions with core MKS or NPHP module components, suggesting they are part of a distinct, CEP-290-associated module. Lastly, we show that families presenting with Oral-Facial-Digital syndrome type 6 (OFD6) have likely pathogenic mutations in CEP-290-dependent TZ proteins, namely Tmem17, Tmem138, and Tmem231. Notably, patient fibroblasts harbouring mutated Tmem17, a protein not yet ciliopathy-associated, display ciliogenesis defects. Together, our findings expand the repertoire of MKS module-associated proteins--including the previously uncharacterised mammalian Tmem80--and suggest an MKS-5 and CEP-290-dependent assembly pathway for building a functional TZ.

Dataset Information

Cell type-specific structural plasticity of the ciliary transition zone in C. elegans.

Publications

Cell type-specific structural plasticity of the ciliary transition zone in C. elegans.

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