A MAP6-Related Protein Is Present in Protozoa and Is Involved in Flagellum Motility

Dacheux, Denis; Landrein, Nicolas; Thonnus, Magali; Gilbert, Guillaume; Sahin, Annelise; Wodrich, Harald; Robinson, Derrick R.; Bonhivers, Mélanie

doi:10.1371/journal.pone.0031344

Cited by 73 publications

(83 citation statements)

References 106 publications

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“…As described previously (Dacheux et al, 2012), whole-cell MAP6-GFP signal in U-2OS cells was diffuse throughout the cytoplasm at 37˚C, and relocalized to cold-stabilized MTs after incubation at 4˚C (Fig. 5A).…”

Section: Results Hsaxo1 Belongs To the Saxo Protein Family And Is Relsupporting

confidence: 80%

“…(A) MEME analysis, using MAP6 and SAXO protein primary sequences of organisms ranging from protozoa to mammals, identified a cysteine-rich domain (pink) and Mn modules (blue) that are shared by MAP6 and SAXO, as well as a SAXO vertebrate specific C-terminal motif (red rectangle). Note that the Mn modules manually annotated in Dacheux et al (Dacheux et al, 2012) are not represented here. Protein scale in amino acid (AA) units is indicated at the bottom.…”

Section: Results Hsaxo1 Belongs To the Saxo Protein Family And Is Relmentioning

confidence: 99%

“…(B) Primary sequence of the hSAXO1 protein with its Mn modules aligned using Clustal W2. The first Mn motif (Mn1) was identified manually as in Dacheux et al (Dacheux et al, 2012). Pink-boxed residues in the N-terminal cysteine-rich domain correspond to the top Logo motif.…”

Section: Results Hsaxo1 Belongs To the Saxo Protein Family And Is Relmentioning

confidence: 99%

“…We have recently identified a MAP6-related family of proteins that we called the SAXO proteins (for stabilizer of axonemal microtubules) (Dacheux et al, 2012). In contrast to the distribution of MAP6 and MAP6d1 genes, which are present only in vertebrates, genes that encode SAXO1 and SAXO2 are present in eukaryotes from protozoa to mammals, but only in ciliated or flagellated organisms.…”

Section: Introductionmentioning

confidence: 99%

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Human FAM154A (SAXO1) is a microtubule-stabilizing protein specific to cilia and related structures

Dacheux

Roger

Bosc

et al. 2015

Journal of Cell Science

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Cilia and flagella are microtubule-based organelles present at the surface of most cells, ranging from protozoa to vertebrates, in which these structures are implicated in processes from morphogenesis to cell motility. In vertebrate neurons, microtubule-associated MAP6 proteins stabilize cold-resistant microtubules through their Mn and Mc modules, and play a role in synaptic plasticity. Although centrioles, cilia and flagella have cold-stable microtubules, MAP6 proteins have not been identified in these organelles, suggesting that additional proteins support this role in these structures. Here, we characterize human FAM154A (hereafter referred to as hSAXO1) as the first human member of a widely conserved family of MAP6-related proteins specific to centrioles and cilium microtubules. Our data demonstrate that hSAXO1 binds specifically to centriole and cilium microtubules. We identify, in vivo and in vitro, hSAXO1 Mn modules as responsible for microtubule binding and stabilization as well as being necessary for ciliary localization. Finally, overexpression and knockdown studies show that hSAXO1 modulates axoneme length. Taken together, our findings suggest a fine regulation of hSAXO1 localization and important roles in cilium biogenesis and function.

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Section: Results Hsaxo1 Belongs To the Saxo Protein Family And Is Relsupporting

confidence: 80%

Section: Results Hsaxo1 Belongs To the Saxo Protein Family And Is Relmentioning

confidence: 99%

Section: Results Hsaxo1 Belongs To the Saxo Protein Family And Is Relmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Human FAM154A (SAXO1) is a microtubule-stabilizing protein specific to cilia and related structures

Dacheux

Roger

Bosc

et al. 2015

Journal of Cell Science

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“…The monoclonal antibody MAb25 (IgG2a) (Pradel et al, 2006), which specifically recognizes the axoneme protein Trypanosoma brucei (Tb)SAXO1 (Dacheux et al, 2012), was used as flagellum marker. The IFT complex B IFT172 protein was recognized using anti-IFT172 mouse monoclonal antibody diluted 1:200 .…”

Section: Immunofluorescence and Live-cell Imagingmentioning

confidence: 99%

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

Fort

Bonnefoy

Kohl

et al. 2016

Journal of Cell Science

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Intraflagellar transport (IFT) is required for construction of most cilia and flagella. Here, we used electron microscopy, immunofluorescence and live video microscopy to show that IFT is absent or arrested in the mature flagellum of Trypanosoma brucei upon RNA interference (RNAi)-mediated knockdown of IFT88 and IFT140, respectively. Flagella assembled prior to RNAi did not shorten, showing that IFT is not essential for the maintenance of flagella length. Although the ultrastructure of the axoneme was not visibly affected, flagellar beating was strongly reduced and the distribution of several flagellar components was drastically modified. The R subunit of the protein kinase A was no longer concentrated in the flagellum but was largely found in the cell body whereas the kinesin 9B motor was accumulating at the distal tip of the flagellum. In contrast, the distal tip protein FLAM8 was dispersed along the flagellum. This reveals that IFT also functions in maintaining the distribution of some flagellar proteins after construction of the organelle is completed.

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Drug Discovery and Development for Kinetoplastid Diseases

Caffrey

Steverding

Ferreira

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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In this article, we review the disease, biology, and biochemistry of kinetoplastids, as well as the new drugs and drug candidates that have entered the clinic in the last decade. We also describe examples of the preclinical exploration of small molecules against various protein targets (e.g. cysteine proteases, the proteasome, and tubulin), as well as cutting‐edge molecular and computational strategies and technologies being brought to bear to discover and develop new antitrypanosomal drugs. For comprehensive descriptions of the disease, biology, and drug therapies prior to 2011, the reader is encouraged to review the article by P.M. Woster that appeared in 2010 in the seventh edition of Burger's Medicinal Chemistry, Drug Discovery, and Development, entitled Antiprotozoal/Antiparasitic Agents.

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A MAP6-Related Protein Is Present in Protozoa and Is Involved in Flagellum Motility

Cited by 73 publications

References 106 publications

Human FAM154A (SAXO1) is a microtubule-stabilizing protein specific to cilia and related structures

Human FAM154A (SAXO1) is a microtubule-stabilizing protein specific to cilia and related structures

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

Drug Discovery and Development for Kinetoplastid Diseases

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