IFT20 Links Kinesin II with a Mammalian Intraflagellar Transport Complex That Is Conserved in Motile Flagella and Sensory Cilia

The intraflagellar transport (IFT) machinery required to build functional cilia consists of a multisubunit complex whose molecular composition, organization, and function are poorly understood. Here, we describe a novel tryptophan-aspartic acid (WD) repeat (WDR) containing IFT protein from Caenorhabditis elegans, DYF-2, that plays a critical role in maintaining the structural and functional integrity of the IFT machinery. We determined the identity of the dyf-2 gene by transgenic rescue of mutant phenotypes and by sequencing of mutant alleles. Loss of DYF-2 function selectively affects the assembly and motility of different IFT components and leads to defects in cilia structure and chemosensation in the nematode. Based on these observations, and the analysis of DYF-2 movement in a Bardet–Biedl syndrome mutant with partially disrupted IFT particles, we conclude that DYF-2 can associate with IFT particle complex B. At the same time, mutations in dyf-2 can interfere with the function of complex A components, suggesting an important role of this protein in the assembly of the IFT particle as a whole. Importantly, the mouse orthologue of DYF-2, WDR19, also localizes to cilia, pointing to an important evolutionarily conserved role for this WDR protein in cilia development and function.

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Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. elegans Sensory Cilia

Current Biology ◽

10.1016/j.cub.2017.04.015 ◽

2017 ◽

Vol 27 (10) ◽

pp. 1448-1461.e7 ◽

Cited By ~ 17

Author(s):

Peishan Yi ◽

Wen-Jun Li ◽

Meng-Qiu Dong ◽

Guangshuo Ou

Keyword(s):

Intraflagellar Transport ◽

C Elegans ◽

Sensory Cilia

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Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons

Nature Cell Biology ◽

10.1038/ncb1186 ◽

2004 ◽

Vol 6 (11) ◽

pp. 1109-1113 ◽

Cited By ~ 258

Author(s):

Joshua J. Snow ◽

Guangshuo Ou ◽

Amy L. Gunnarson ◽

M. Regina S. Walker ◽

H. Mimi Zhou ◽

...

Keyword(s):

Intraflagellar Transport ◽

C Elegans ◽

Sensory Cilia

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Interaction of mouse TTC30/DYF-1 with multiple intraflagellar transport complex B proteins and KIF17

Experimental Cell Research ◽

10.1016/j.yexcr.2013.06.010 ◽

2013 ◽

Vol 319 (14) ◽

pp. 2275-2281 ◽

Cited By ~ 7

Author(s):

Paul W. Howard ◽

Shall F. Jue ◽

Richard A. Maurer

Keyword(s):

Intraflagellar Transport ◽

Transport Complex

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Interactions between TULP3 tubby domain cargo site and ARL13B amphipathic helix promote lipidated protein transport to cilia

10.1101/2021.05.25.445488 ◽

2021 ◽

Author(s):

Vivek Reddy Palicharla ◽

Sun-hee Hwang ◽

Bandarigoda N. Somatilaka ◽

Hemant B. Badgandi ◽

Emilie Legue ◽

...

Keyword(s):

Protein Transport ◽

Transmembrane Proteins ◽

Intraflagellar Transport ◽

Amphipathic Helix ◽

Cargo Transport ◽

Family Protein ◽

Associated Proteins ◽

Sorting Motif ◽

Necessary And Sufficient ◽

Transport Complex

The tubby family protein-TULP3 coordinates with the intraflagellar transport complex-A (IFT-A) in trafficking certain transmembrane proteins to cilia. These transmembrane cargoes have short motifs that are necessary and sufficient for TULP3-mediated trafficking. However, whether TULP3 regulates trafficking of membrane-associated proteins is not well understood. Here we show that TULP3 is required for transport of the atypical GTPase ARL13B into cilia, and for ciliary enrichment of ARL13B-dependent farnesylated and myristoylated proteins. ARL13B transport requires TULP3 binding to IFT-A core but not to phosphoinositides, unlike transmembrane cargo transport that requires binding to both by TULP3. A conserved lysine in TULP3's tubby domain mediates direct ARL13B binding and trafficking of lipidated and transmembrane cargoes. An N-terminal amphipathic helix in ARL13B flanking the palmitoylation site mediates binding to TULP3 and directs trafficking to cilia even in absence of palmitoylation and RVxP sorting motif. Therefore, TULP3 transports transmembrane proteins and ARL13B into cilia by capture of short sequences through a shared tubby domain site.

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MAK and CCRK kinases regulate kinesin-2 motility in C. elegans neuronal cilia

10.1101/209221 ◽

2017 ◽

Author(s):

Peishan Yi ◽

Chao Xie ◽

Guangshuo Ou

Keyword(s):

Cell Cycle ◽

Sensory Neurons ◽

Intraflagellar Transport ◽

Time Lapse ◽

Genetic Screen ◽

Forward Genetic Screen ◽

C Elegans ◽

Neuronal Cilia ◽

Sensory Cilia

AbstractKinesin-2 motors power the anterograde intraflagellar transport (IFT), a highly ordered process that assembles and maintains cilia. It remains elusive how kinesin-2 motors are regulated in vivo. Here we perform forward genetic screen to isolate suppressors that rescue the ciliary defects in the constitutive active mutation of OSM-3-kinesin (G444E) in C. elegans sensory neurons. We identify the C. elegans DYF-5 and DYF-18, which encode the homologs of mammalian male germ cell-associated kinase (MAK) and cell cycle-related kinase (CCRK). Using time-lapse fluorescence microscopy, we show that DYF-5 and DYF-18 are IFT cargo molecules and are enriched at the distal segments of sensory cilia. Mutations of dyf-5 and dyf-18 generate the elongated cilia and ectopic localization of kinesin-II at the ciliary distal segments. Genetic analyses reveal that dyf-5 and dyf-18 are also important for stabilizing the interaction between IFT particle and OSM-3-kinesin. Our data suggest that DYF-5 and DYF-18 act in the same pathway to promote handover between kinesin-II and OSM-3 in sensory cilia.

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