2018
DOI: 10.7554/elife.39655
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Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

Abstract: 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 ex… Show more

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Cited by 43 publications
(142 citation statements)
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References 63 publications
(102 reference statements)
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“…Although there are several common features of IFT between model organisms, there are also key differences. In Chlamydomonas, kinesin-2 appears to mainly diffuse back to the ciliary base (Engel et al, 2012), whereas, in metazoans, kinesin-2 motors appear to be recycled to the ciliary base predominantly through retrograde IFT (Mijalkovic et al, 2017;Signor et al, 1999;Vuolo et al, 2018;Williams et al, 2014). Interestingly, in C. elegans, an additional dynein heavy chain, i.e.…”
Section: Structure and Composition Of Dynein-2mentioning
confidence: 99%
See 1 more Smart Citation
“…Although there are several common features of IFT between model organisms, there are also key differences. In Chlamydomonas, kinesin-2 appears to mainly diffuse back to the ciliary base (Engel et al, 2012), whereas, in metazoans, kinesin-2 motors appear to be recycled to the ciliary base predominantly through retrograde IFT (Mijalkovic et al, 2017;Signor et al, 1999;Vuolo et al, 2018;Williams et al, 2014). Interestingly, in C. elegans, an additional dynein heavy chain, i.e.…”
Section: Structure and Composition Of Dynein-2mentioning
confidence: 99%
“…WDR34 and WDR60 form a heterodimer (Asante et al, 2014;Hamada et al, 2018;Toropova et al, 2019;Vuolo et al, 2018) (see poster). Their C-terminal β-propeller domains each bind a copy of the heavy chain, and their extended N-terminal regions are held together by an array of light chain dimers (Toropova et al, 2019).…”
Section: Structure and Composition Of Dynein-2mentioning
confidence: 99%
“…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%
“…Interestingly, dynein-2 heavy chain immunoprecipitated with IFT172 migrates differently by SDS-PAGE compared to that from crude extract, suggesting that it could be differentially modified [ 44 ]. Additional IFT-B proteins have been associated with dynein-2 in trypanosomes (IFT22/25/27) [ [139] , [140] , [141] ] and mammalian cells (IFT25/54/57/74/88/172) [ 86 ].…”
Section: The Retrograde Motormentioning
confidence: 99%
“…Dysfunction of IFT-A is typically associated with short cilia with accumulations at their tips, similar to the cellular phenotype of dynein-2 mutants [ 31 ]. The IFT-A proteins IFT139 and IFT140 have been found to co-immmunoprecipitate with dynein-2 in C. reinhardtii [ 75 ] and mammalian cells [ 135 ], respectively. In general, because the IFT-A and IFT-B proteins play multiple roles in IFT train assembly, cargo binding, and ciliogenesis, dissecting their specific contribution to dynein-2 regulation is an ongoing challenge.…”
Section: Introductionmentioning
confidence: 99%