Intraflagellar Transport Complex A Genes Differentially Regulate Cilium Formation and Transition Zone Gating

Scheidel, Noémie; Blacque, Oliver E.

doi:10.1016/j.cub.2018.08.017

Cited by 41 publications

(39 citation statements)

References 43 publications

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“…Indeed, it is quite likely that the role of dynein-2 in transition zone structure is a result of its established role in IFT. Recent data from the Blacque lab using IFT-A mutants ( Scheidel and Blacque, 2018 ) and from the Leroux labs using a temperature sensitive allele of the dynein-2 heavy chain (Jensen et al, personal communication ), both using C. elegans , provides support for this interpretation.…”

Section: Discussionmentioning

confidence: 96%

Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

Vuolo

Stevenson

Heesom

et al. 2018

eLife

112

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The dynein-2 microtubule motor is the retrograde motor for intraflagellar transport. Mutations in dynein-2 components cause skeletal ciliopathies, notably Jeune syndrome. Dynein-2 contains a heterodimer of two non-identical intermediate chains, WDR34 and WDR60. Here, we use knockout cell lines to demonstrate that each intermediate chain has a distinct role in cilium function. Using quantitative proteomics, we show that WDR34 KO cells can assemble a dynein-2 motor complex that binds IFT proteins yet fails to extend an axoneme, indicating complex function is stalled. In contrast, WDR60 KO cells do extend axonemes but show reduced assembly of dynein-2 and binding to IFT proteins. Both proteins are required to maintain a functional transition zone and for efficient bidirectional intraflagellar transport. Our results indicate that the subunit asymmetry within the dynein-2 complex is matched with a functional asymmetry between the dynein-2 intermediate chains. Furthermore, this work reveals that loss of function of dynein-2 leads to defects in transition zone architecture, as well as intraflagellar transport.

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Section: Discussionmentioning

confidence: 96%

Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

Vuolo

Stevenson

Heesom

et al. 2018

eLife

112

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“…Recently, new insights into IFT trafficking revealed an unexpected role for IFT-A and dynein-2 in maintaining compartmentalisation of the transition zone and, thus, of the ciliary structure in C. elegans and human cells (Jensen et al, 2018;Vuolo et al, 2018;Scheidel and Blacque, 2018). The transition zone consists of a densely packed domain containing multiple proteins that are assembled in a tightly regulated process (see Box 1 and poster).…”

Section: Dynein-2 and The Ciliary Transition Zonementioning

confidence: 99%

“…It is uncertain how dynein-2 mediates transition zone assembly but it might involve its association with the IFT-A cargo adapter complex (Scheidel and Blacque, 2018). In C. elegans, analysis of IFT-A mutants indicated that IFT-A subunits play different roles in cilia entry and/or export of transition zone components in the cilia.…”

Section: Dynein-2 and The Ciliary Transition Zonementioning

confidence: 99%

Cytoplasmic dynein-2 at a glance

Vuolo

Stevenson

Mukhopadhyay

et al. 2020

Journal of Cell Science

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Cytoplasmic dynein-2 is a motor protein complex that drives the movement of cargoes along microtubules within cilia, facilitating the assembly of these organelles on the surface of nearly all mammalian cells. Dynein-2 is crucial for ciliary function, as evidenced by deleterious mutations in patients with skeletal abnormalities. Longstanding questions include how the dynein-2 complex is assembled, regulated, and switched between active and inactive states. A combination of model organisms, in vitro cell biology, live-cell imaging, structural biology and biochemistry has advanced our understanding of the dynein-2 motor. In this Cell Science at a Glance article and the accompanying poster, we discuss the current understanding of dynein-2 and its roles in ciliary assembly and function.

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“…It will be interesting to decipher if passage through the transition zone requires a conformational change in the IFT train or Y-link. Recent studies show that mutations in IFT-A and dynein-2 subunits can perturb the localization of transition zone proteins, highlighting a connection between IFT and transition zone integrity [ [85] , [86] , [87] ].…”

Section: Navigating the Microtubule Doublet And Transition Zonementioning

confidence: 99%

Intraflagellar transport trains and motors: Insights from structure

Webb

Mukhopadhyay

Roberts

2020

Seminars in Cell & Developmental Biology

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Intraflagellar transport (IFT) sculpts the proteome of cilia and flagella; the antenna-like organelles found on the surface of virtually all human cell types. By delivering proteins to the growing ciliary tip, recycling turnover products, and selectively transporting signalling molecules, IFT has critical roles in cilia biogenesis, quality control, and signal transduction. IFT involves long polymeric arrays, termed IFT trains, which move to and from the ciliary tip under the power of the microtubule-based motor proteins kinesin-II and dynein-2. Recent top-down and bottom-up structural biology approaches are converging on the molecular architecture of the IFT train machinery. Here we review these studies, with a focus on how kinesin-II and dynein-2 assemble, attach to IFT trains, and undergo precise regulation to mediate bidirectional transport.

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Intraflagellar Transport Complex A Genes Differentially Regulate Cilium Formation and Transition Zone Gating

Cited by 41 publications

References 43 publications

Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

Cytoplasmic dynein-2 at a glance

Intraflagellar transport trains and motors: Insights from structure

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