Shulin packages axonemal outer dynein arms for ciliary targeting

Mali, Girish R.; Ali, Ferdos Abid; Lau, C.K.; Begum, Farida; Skehel, J. Mark; Carter, Andrew P.

doi:10.1101/2020.09.04.282897

Cited by 9 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This core is expanded by an additional heavy chain (α-HC) appended to the tail of β-HC and the calcium-responsive light chain LC4 bound to the tail of γ-HC. The other axonemal-specific light chains, LC3 and LC5, may interact with the heavy chain tails preceding the motor linkers where our map is least well-resolved 49 .…”

Section: Discussionmentioning

confidence: 99%

Structure of a microtubule-bound axonemal dynein

2021

View full text Add to dashboard Cite

Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating, a process critical for cellular motility and extracellular fluid flow. Axonemal dyneins are evolutionarily and biochemically distinct from cytoplasmic dyneins that transport cargo, and the mechanisms regulating their localization and function are poorly understood. Here, we report a single-particle cryo-EM reconstruction of a three-headed axonemal dynein natively bound to doublet microtubules isolated from cilia. The slanted conformation of the axonemal dynein causes interaction of its motor domains with the neighboring dynein complex. Our structure shows how a heterotrimeric docking complex specifically localizes the linear array of axonemal dyneins to the doublet microtubule by directly interacting with the heavy chains. Our structural analysis establishes the arrangement of conserved heavy, intermediate and light chain subunits, and provides a framework to understand the roles of individual subunits and the interactions between dyneins during ciliary waveform generation.

show abstract

Section: Discussionmentioning

confidence: 99%

Structure of a microtubule-bound axonemal dynein

2021

View full text Add to dashboard Cite

show abstract

“…The linkage of an NDK domain to the DUF4701 domain in non-mammalian Daap1 orthologs suggest the possibility that these two protein domains may act in concert, and it is tempting to speculate that the NDK domain of Daap1 in non-mammalian vertebrates may explain the absence of either Nme8 or Nme9 in those genomes. Interestingly, a very recent report describes the discovery of novel NDK domain protein in Tetrahymena with a specific role in stabilizing ODA dyneins in an inactive conformation for targeting to axonemes ( Mali et al, 2020 ). It is possible then that Daap1 plays a similar role in Xenopus .…”

Section: Discussionmentioning

confidence: 99%

Functional partitioning of a liquid-like organelle during assembly of axonemal dyneins

Lee

Cox

Papoulas

et al. 2020

eLife

View full text Add to dashboard Cite

Ciliary motility is driven by axonemal dyneins that are assembled in the cytoplasm before deployment to cilia. Motile ciliopathy can result from defects in the dyneins themselves or from defects in factors required for their cytoplasmic pre-assembly. Recent work demonstrates that axonemal dyneins, their specific assembly factors, and broadly acting chaperones are concentrated in liquid-like organelles in the cytoplasm called DynAPs (Dynein Axonemal Particles). Here, we use in vivo imaging in Xenopus to show that inner dynein arm (IDA) and outer dynein arm (ODA) subunits are partitioned into non-overlapping sub-regions within DynAPs. Using affinity purification mass-spectrometry of in vivo interaction partners, we also identify novel partners for inner and outer dynein arms. Among these, we identify C16orf71/Daap1 as a novel axonemal dynein regulator. Daap1 interacts with ODA subunits, localizes specifically to the cytoplasm, is enriched in DynAPs, and is required for the deployment of ODAs to axonemes. Our work reveals a new complexity in the structure and function of a cell-type specific liquid-like organelle that is directly relevant to human genetic disease.

show abstract

“…Moreover, is there any negative regulator that helps keep dynein in the autoinhibited conformation in vivo? While we still do not know if such a regulator exists for cytoplasmic dynein, a recent study using Tetrahymena has identified a novel axonemal dynein-binding protein, Shulin, as a regulator that keeps axonemal dynein in an inactivate conformation before it is delivered to cilia (Mali et al, 2020). While both biochemical and genetic approaches can be powerful, genetic screens in A. nidulans have been highly valuable in identifying new proteins involved in dyneinmediated intracellular transport (Osmani et al, 1990;Xiang et al, 1995;Efimov and Morris, 2000;Yao et al, 2014;Zhang et al, 2014;Salogiannis et al, 2016).…”

Section: Future Directionsmentioning

confidence: 99%

Cargo-Mediated Activation of Cytoplasmic Dynein in vivo

Xiang

Qiu

2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Cytoplasmic dynein-1 is a minus-end-directed microtubule motor that transports a variety of cargoes including early endosomes, late endosomes and other organelles. In many cell types, dynein accumulates at the microtubule plus end, where it interacts with its cargo to be moved toward the minus end. Dynein binds to its various cargoes via the dynactin complex and specific cargo adapters. Dynactin and some of the coiledcoil-domain-containing cargo adapters not only link dynein to cargo but also activate dynein motility, which implies that dynein is activated by its cellular cargo. Structural studies indicate that a dynein dimer switches between the autoinhibited phi state and an open state; and the binding of dynactin and a cargo adapter to the dynein tails causes the dynein motor domains to have a parallel configuration, allowing dynein to walk processively along a microtubule. Recently, the dynein regulator LIS1 has been shown to be required for dynein activation in vivo, and its mechanism of action involves preventing dynein from switching back to the autoinhibited state. In this review, we will discuss our current understanding of dynein activation and point out the gaps of knowledge on the spatial regulation of dynein in live cells. In addition, we will emphasize the importance of studying a complete set of dynein regulators for a better understanding of dynein regulation in vivo.

show abstract

Shulin packages axonemal outer dynein arms for ciliary targeting

Cited by 9 publications

References 45 publications

Structure of a microtubule-bound axonemal dynein

Structure of a microtubule-bound axonemal dynein

Functional partitioning of a liquid-like organelle during assembly of axonemal dyneins

Cargo-Mediated Activation of Cytoplasmic Dynein in vivo

Contact Info

Product

Resources

About