<i>Drosophila</i>sensory cilia lacking MKS-proteins exhibit striking defects during development but only subtle defects in adults

Pratt, Metta B.; Titlow, Josh; Davis, Ilan; Barker, Amy R.; Dawe, Helen R.; Raff, Jordan W.; Roque, Hélio

doi:10.1101/058081

Cited by 4 publications

(5 citation statements)

References 55 publications

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“…We propose that Rpgrip1 serves as a safeguard mechanism because, in comparison to invertebrates, the importance of functional cilia, especially of primary cilia, is far greater in vertebrates. For example, C. elegans and Drosophila have only a few cell types which are able to form cilia (Inglis et al , ; Pratt et al , ) and these two organisms develop largely properly without cilia (Apfeld & Kenyon, ; Basto et al , ; Bae & Barr, ). As our data demonstrate, Rpgrip1 is able to partially compensate for an impaired function of Rpgrip1l.…”

Section: Discussionmentioning

confidence: 99%

Cell type‐specific regulation of ciliary transition zone assembly in vertebrates

et al. 2018

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Ciliopathies are life‐threatening human diseases caused by defective cilia. They can often be traced back to mutations of genes encoding transition zone (TZ) proteins demonstrating that the understanding of TZ organisation is of paramount importance. The TZ consists of multimeric protein modules that are subject to a stringent assembly hierarchy. Previous reports place Rpgrip1l at the top of the TZ assembly hierarchy in Caenorhabditis elegans. By performing quantitative immunofluorescence studies in RPGRIP1L−/− mouse embryos and human embryonic cells, we recognise a different situation in vertebrates in which Rpgrip1l deficiency affects TZ assembly in a cell type‐specific manner. In cell types in which the loss of Rpgrip1l alone does not affect all modules, additional truncation or removal of vertebrate‐specific Rpgrip1 results in an impairment of all modules. Consequently, Rpgrip1l and Rpgrip1 synergistically ensure the TZ composition in several vertebrate cell types, revealing a higher complexity of TZ assembly in vertebrates than in invertebrates.

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Section: Discussionmentioning

confidence: 99%

Cell type‐specific regulation of ciliary transition zone assembly in vertebrates

et al. 2018

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“…For this reason, the assembly and function of the TZ is a hot topic in biomedical research. A lot of proteins participate in TZ assembly and/or function as ciliary gatekeepers at the TZ (Craige et al, 2010;Chih et al, 2011;Garcia-Gonzalo et al, 2011;Huang et al, 2011;Sang et al, 2011;Williams et al, 2011;Aubusson-Fleury et al, 2012;Cevik et al, 2013;Wang et al, 2013;Awata et al, 2014;Basiri et al, 2014;Klinger et al, 2014;Tuz et al, 2014;Bachmann-Gagescu et al, 2015;Barbelanne et al, 2015b;Damerla et al, 2015;Roberson et al, 2015;Yee et al, 2015;Lambacher et al, 2016;Li et al, 2016;Pratt et al, 2016;Slaats et al, 2016;Vieillard et al, 2016;Wei et al, 2016;Dyson et al, 2017;Lu et al, 2017;Schou et al, 2017;Shi et al, 2017;Takao et al, 2017;Jensen et al, 2018;Scheidel and Blacque, 2018;Wiegering et al, 2018a;Jack et al, 2019;Lapart et al, 2019;Lewis et al, 2019). However, the relationships between these proteins and hence the mechanisms underlying ciliary gating at the TZ remain largely elusive.…”

Section: The Role Of Tz Proteins In Ciliary Gatingmentioning

confidence: 99%

Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone

Wiegering

Dildrop

Vesque

et al. 2021

MBoC

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A range of severe human diseases called ciliopathies are caused by the dysfunction of primary cilia. Primary cilia are cytoplasmic protrusions consisting of the basal body (BB), the axoneme and the transition zone (TZ). The BB is a modified mother centriole from which the axoneme, the microtubule-based ciliary scaffold, is formed. At the proximal end of the axoneme, the TZ functions as the ciliary gate governing ciliary protein entry and exit. Since ciliopathies often develop due to mutations in genes encoding proteins that localise to the TZ, the understanding of the mechanisms underlying TZ function is of eminent importance. Here, we show that the ciliopathy protein Rpgrip1l governs ciliary gating by ensuring the proper amount of Cep290 at the vertebrate TZ. Further, we identified the flavonoid eupatilin as a potential agent to tackle ciliopathies caused by mutations in RPGRIP1L as it rescues ciliary gating in the absence of Rpgrip1l.

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“…In Drosophila, the Cep290 gene produces only one protein isoform and the protein localises to transition zones of most cilia types, being required for cilia assembly ( Figure 3E; 29 ), suggesting it might be a core component of most transition zones. However, recently, CEP290 was also: i) implicated in central ring formation in the C. elegans transition zone 54 , ii) found in the lumen of the proximal part of the transition zone in the primary cilia of human retinal pigmented epithelial (hRPE) cells 55 and iii) found to occupy an inner region of the transition zone overlapping with axonemal MTs 56,57 in Drosophila, upon using C-terminally tagged CEP290. Altogether this evidence suggests CEP290 localises differently in different organisms.…”

Section: Cep290 Is Required To Form Diverse Linker Structures In the mentioning

confidence: 99%

Differential regulation of transition zone and centriole proteins contributes to ciliary base diversity

et al. 2018

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Cilia are evolutionarily conserved structures with many sensory and motility-related functions. The ciliary base, composed of the basal body and the transition zone, is critical for cilia assembly and function, but its contribution to cilia diversity remains unknown. Hence, we generated a high-resolution structural and biochemical atlas of the ciliary base of four functionally distinct neuronal and sperm cilia types within an organism, Drosophila melanogaster. We uncovered a common scaffold and diverse structures associated with different localization of 15 evolutionarily conserved components. Furthermore, CEP290 (also known as NPHP6) is involved in the formation of highly diverse transition zone links. In addition, the cartwheel components SAS6 and ANA2 (also known as STIL) have an underappreciated role in basal body elongation, which depends on BLD10 (also known as CEP135). The differential expression of these cartwheel components contributes to diversity in basal body length. Our results offer a plausible explanation to how mutations in conserved ciliary base components lead to tissue-specific diseases.

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Drosophilasensory cilia lacking MKS-proteins exhibit striking defects during development but only subtle defects in adults

Cited by 4 publications

References 55 publications

Cell type‐specific regulation of ciliary transition zone assembly in vertebrates

Cell type‐specific regulation of ciliary transition zone assembly in vertebrates

Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone

Differential regulation of transition zone and centriole proteins contributes to ciliary base diversity

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