Integrated control of axonemal dynein AAA+ motors

King, Stephen M.

doi:10.1016/j.jsb.2012.02.013

Cited by 38 publications

(34 citation statements)

References 80 publications

(95 reference statements)

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“…Only a few cases have been reported where proteins are thought to interact directly with the motor domain of a dynein (53)(54)(55). Based on biochemical evidence, Patel-King and King (55) have reported that the 22-kDa LC1 likely forms a bridge between the ODA γ HC motor domain and the DMT in axonemes, possibly providing limiting doublet sliding in the axonemal bend.…”

Section: Discussionmentioning

confidence: 99%

Cryoelectron tomography reveals doublet-specific structures and unique interactions in the I1 dynein

Heuser

Barber

Lin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

133

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Cilia and flagella are highly conserved motile and sensory organelles in eukaryotes, and defects in ciliary assembly and motility cause many ciliopathies. The two-headed I1 inner arm dynein is a critical regulator of ciliary and flagellar beating. To understand I1 architecture and function better, we analyzed the 3D structure and composition of the I1 dynein in Chlamydomonas axonemes by cryoelectron tomography and subtomogram averaging. Our data revealed several connections from the I1 dynein to neighboring structures that are likely to be important for assembly and/or regulation, including a tether linking one I1 motor domain to the doublet microtubule and doublet-specific differences potentially contributing to the asymmetrical distribution of dynein activity required for ciliary beating. We also imaged three I1 mutants and analyzed their polypeptide composition using 2D gel-based proteomics. Structural and biochemical comparisons revealed the likely location of the regulatory IC138 phosphoprotein and its associated subcomplex. Overall, our studies demonstrate that I1 dynein is connected to multiple structures within the axoneme, and therefore ideally positioned to integrate signals that regulate ciliary motility.dynein f | flagella C ilia and flagella are highly conserved organelles with roles in cellular movement and signal transduction. In humans, defects in cilia can lead to a number of diseases, such as polycystic kidney disease and primary ciliary dyskinesia (1, 2). The axoneme core of most motile cilia and flagella consists of nine doublet microtubules (DMTs) surrounding two single microtubules (MTs) known as the central pair complex (CPC) (Fig. 1). DMTs are highly periodic with a 96-nm-long unit that repeats along the MT length. They are decorated with two rows of dynein motors, the inner dynein arms (IDAs) and the outer dynein arms (ODAs), which drive MT sliding and axoneme bending (3). Generating the diverse ciliary and flagellar waveforms requires the precise coordination of the activity of thousands of dynein motors within a single organelle (4).The primary signaling pathway known to regulate dynein function in axonemes involves signals traveling from the CPC through radial spokes (RSs) to the IDAs and ODAs (reviewed in 5, 6). Many CPC and RS mutants are paralyzed (7). However, MT sliding can be restored to WT levels in isolated CPC/RS mutant axonemes using protein kinase inhibitors (8, 9). These observations, together with biochemical evidence of phosphorylation of dynein subunits, have implicated the dyneins as a major signaling target of the CPC/RS signaling pathway (10, 11). However, the regulatory mechanisms and physical interactions that participate in signal transduction to the dynein targets are not well understood.Isolated axonemes require only ATP for reactivation, suggesting that direct interactions between the dyneins and their regulators are physically built into the axoneme (4). Therefore, studies that visualize axonemal structures and their connections at high resolution can provide ...

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Section: Discussionmentioning

confidence: 99%

Cryoelectron tomography reveals doublet-specific structures and unique interactions in the I1 dynein

Heuser

Barber

Lin

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

133

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“…The CMF22 IQ motif is of particular interest because it links CMF22 to potential functions in Ca 2ϩ regulation of flagellar motility, which is conserved across diverse phyla and likely has roots in regulatory mechanisms that appeared early in eukaryotic evolution. Chemotaxis of mammalian sperm as well as flagellated protists is dependent upon modulation of the motility apparatus in response to extracellular cues, using Ca 2ϩ as the second messenger (12,(77)(78)(79)(80)(81). Targets of Ca 2ϩ are not well understood, but pioneering studies in Chlamydomonas recently identified three axonemal protein complexes that bind calmodulin and are predicted to function in Ca 2ϩ regulation (82)(83)(84).…”

Section: Discussionmentioning

confidence: 99%

CMF22 Is a Broadly Conserved Axonemal Protein and Is Required for Propulsive Motility in Trypanosoma brucei

et al. 2013

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bThe eukaryotic flagellum (or cilium) is a broadly conserved organelle that provides motility for many pathogenic protozoa and is critical for normal development and physiology in humans. Therefore, defining core components of motile axonemes enhances understanding of eukaryotic biology and provides insight into mechanisms of inherited and infectious diseases in humans. In this study, we show that component of motile flagella 22 (CMF22) is tightly associated with the flagellar axoneme and is likely to have been present in the last eukaryotic common ancestor. The CMF22 amino acid sequence contains predicted IQ and ATPase associated with a variety of cellular activities (AAA) motifs that are conserved among CMF22 orthologues in diverse organisms, hinting at the importance of these domains in CMF22 function. Knockdown by RNA interference (RNAi) and rescue with an RNAi-immune mRNA demonstrated that CMF22 is required for propulsive cell motility in Trypanosoma brucei. Loss of propulsive motility in CMF22-knockdown cells was due to altered flagellar beating patterns, rather than flagellar paralysis, indicating that CMF22 is essential for motility regulation and likely functions as a fundamental regulatory component of motile axonemes. CMF22 association with the axoneme is weakened in mutants that disrupt the nexin-dynein regulatory complex, suggesting potential interaction with this complex. Our results provide insight into the core machinery required for motility of eukaryotic flagella.

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“…While the levels of the inner dynein arm I1 subunits IC138 (Bower et al, 2009) and IC140 (Perrone et al, 1998;Yang and Sale, 1998), microtubule doublet inner junction protein FAP20 , outer dynein arm components LC1 and IC69 (King, 2012), radial spoke protein RSP3 (Yang et al, 2006), and axonemal protein MBO2 (Tam and Lefebvre, 2002) were near wild-type levels, the amount of IC97 ) was significantly reduced in the ift57-1 mutant flagella (Fig. 8).…”

Section: Ift57 Is Required For Establishing Normal Flagellar Waveformsmentioning

confidence: 92%

IFT57 stabilizes the assembled intraflagellar transport complex and mediates transport of motility-related flagellar cargo

Jiang

Hernandez

et al. 2017

Journal of Cell Science

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Intraflagellar transport (IFT) is essential for the assembly and maintenance of flagella and cilia. Recent biochemical studies have shown that IFT complex B (IFT-B) is comprised of two subcomplexes, IFT-B1 and IFT-B2. The IFT-B2 subunit IFT57 lies at the interface between IFT-B1 and IFT-B2. Here, using a Chlamydomonas reinhardtii mutant for IFT57, we tested whether IFT57 is required for IFT-B complex assembly by bridging IFT-B1 and IFT-B2 together. In the ift57-1 mutant, levels of IFT57 and other IFT-B proteins were greatly reduced at the whole-cell level. However, strikingly, in the protease-free flagellar compartment, while the level of IFT57 was reduced, the levels of other IFT particle proteins were not concomitantly reduced but were present at the wild-type level. The IFT movement of the IFT57-deficient IFT particles was also unchanged. Moreover, IFT57 depletion disrupted the flagellar waveform, leading to cell swimming defects. Analysis of the mutant flagellar protein composition showed that certain axonemal proteins were altered. Taken together, these findings suggest that IFT57 does not play an essential structural role in the IFT particle complex but rather functions to prevent it from degradation. Additionally, IFT57 is involved in transporting specific motility-related proteins.

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Integrated control of axonemal dynein AAA+ motors

Cited by 38 publications

References 80 publications

Cryoelectron tomography reveals doublet-specific structures and unique interactions in the I1 dynein

Cryoelectron tomography reveals doublet-specific structures and unique interactions in the I1 dynein

CMF22 Is a Broadly Conserved Axonemal Protein and Is Required for Propulsive Motility in Trypanosoma brucei

IFT57 stabilizes the assembled intraflagellar transport complex and mediates transport of motility-related flagellar cargo

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