Dataset Information

Dilatory is a Drosophila protein related to AZI1 (CEP131) that is located at the ciliary base and required for cilium formation.

ABSTRACT: A significant number of ciliary disease genes have been found to encode proteins that localise to the basal body. By contrast, a large number of basal-body-associated proteins remain to be characterised. Here, we report the identification of a new basal body protein that is required for ciliogenesis in Drosophila. Dilatory (DILA) is a predicted coiled-coil protein homologous to vertebrate AZI1 (also known as CEP131). Mutations in dila specifically exhibit defects in ciliated cells (sensory neurons and sperm). Several features of the neuronal phenotype suggest a defect in intraflagellar transport. In sensory neuron cilia, DILA protein localises to the ciliary base, including the basal body and putative transition zone, and it interacts genetically with the ciliary coiled-coil protein, Uncoordinated. These data implicate DILA in regulating intraflagellar transport at the base of sensory cilia.

SUBMITTER: Ma L

PROVIDER: S-EPMC3138703 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Dilatory is a Drosophila protein related to AZI1 (CEP131) that is located at the ciliary base and required for cilium formation.

Ma Lina L Jarman Andrew P AP

Journal of cell science 20110712 Pt 15

A significant number of ciliary disease genes have been found to encode proteins that localise to the basal body. By contrast, a large number of basal-body-associated proteins remain to be characterised. Here, we report the identification of a new basal body protein that is required for ciliogenesis in Drosophila. Dilatory (DILA) is a predicted coiled-coil protein homologous to vertebrate AZI1 (also known as CEP131). Mutations in dila specifically exhibit defects in ciliated cells (sensory neuro ...[more]

PMID: 21750193

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Project description:Defects in cilium and centrosome function result in a spectrum of clinically-related disorders, known as ciliopathies. However, the complex molecular composition of these structures confounds functional dissection of what any individual gene product is doing under normal and disease conditions. As part of an siRNA screen for genes involved in mammalian ciliogenesis, we and others have identified the conserved centrosomal protein Azi1/Cep131 as required for cilia formation, supporting previous Danio rerio and Drosophila melanogaster mutant studies. Acute loss of Azi1 by knock-down in mouse fibroblasts leads to a robust reduction in ciliogenesis, which we rescue by expressing siRNA-resistant Azi1-GFP. Localisation studies show Azi1 localises to centriolar satellites, and traffics along microtubules becoming enriched around the basal body. Azi1 also localises to the transition zone, a structure important for regulating traffic into the ciliary compartment. To study the requirement of Azi1 during development and tissue homeostasis, Azi1 null mice were generated (Azi1(Gt/Gt)). Surprisingly, Azi1(Gt/Gt) MEFs have no discernible ciliary phenotype and moreover are resistant to Azi1 siRNA knock-down, demonstrating that a compensation mechanism exists to allow ciliogenesis to proceed despite the lack of Azi1. Cilia throughout Azi1 null mice are functionally normal, as embryonic patterning and adult homeostasis are grossly unaffected. However, in the highly specialised sperm flagella, the loss of Azi1 is not compensated, leading to striking microtubule-based trafficking defects in both the manchette and the flagella, resulting in male infertility. Our analysis of Azi1 knock-down (acute loss) versus gene deletion (chronic loss) suggests that Azi1 plays a conserved, but non-essential trafficking role in ciliogenesis. Importantly, our in vivo analysis reveals Azi1 mediates novel trafficking functions necessary for flagellogenesis. Our study highlights the importance of both acute removal of a protein, in addition to mouse knock-out studies, when functionally characterising candidates for human disease.

Dataset Information

Dilatory is a Drosophila protein related to AZI1 (CEP131) that is located at the ciliary base and required for cilium formation.

Publications

Dilatory is a Drosophila protein related to AZI1 (CEP131) that is located at the ciliary base and required for cilium formation.

Similar Datasets

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