scholarly journals Consensus nomenclature for dyneins and associated assembly factors

2022 ◽  
Vol 221 (2) ◽  
Author(s):  
Bryony Braschi ◽  
Heymut Omran ◽  
George B. Witman ◽  
Gregory J. Pazour ◽  
K. Kevin Pfister ◽  
...  
Keyword(s):  
Molecular Motors ◽  
Model Organism ◽  
Intraflagellar Transport ◽  
Flagellar Motility ◽  
Gene Nomenclature ◽  
Ciliary Function ◽  
Unicellular Green Alga ◽  
Genes Encoding ◽  
Clinical Interest ◽  
Axonemal Dynein

Dyneins are highly complex, multicomponent, microtubule-based molecular motors. These enzymes are responsible for numerous motile behaviors in cytoplasm, mediate retrograde intraflagellar transport (IFT), and power ciliary and flagellar motility. Variants in multiple genes encoding dyneins, outer dynein arm (ODA) docking complex subunits, and cytoplasmic factors involved in axonemal dynein preassembly (DNAAFs) are associated with human ciliopathies and are of clinical interest. Therefore, clear communication within this field is particularly important. Standardizing gene nomenclature, and basing it on orthology where possible, facilitates discussion and genetic comparison across species. Here, we discuss how the human gene nomenclature for dyneins, ODA docking complex subunits, and DNAAFs has been updated to be more functionally informative and consistent with that of the unicellular green alga Chlamydomonas reinhardtii, a key model organism for studying dyneins and ciliary function. We also detail additional nomenclature updates for vertebrate-specific genes that encode dynein chains and other proteins involved in dynein complex assembly.

Molecular basis of ciliary defects caused by compound heterozygous IFT144/WDR19 mutations found in cranioectodermal dysplasia

2021 ◽  
Author(s):  
Yamato Ishida ◽  
Takuya Kobayashi ◽  
Shuhei Chiba ◽  
Yohei Katoh ◽  
Kazuhisa Nakayama
Keyword(s):  
Protein Trafficking ◽  
Primary Cilia ◽  
Intraflagellar Transport ◽  
Missense Variant ◽  
Cellular Level ◽  
Compound Heterozygous ◽  
Hypomorphic Allele ◽  
Genes Encoding ◽  
Specific Proteins ◽  
Compound Heterozygous Mutations

Abstract Primary cilia contain specific proteins to achieve their functions as cellular antennae. Ciliary protein trafficking is mediated by the intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes. Mutations in genes encoding the IFT-A subunits (IFT43, IFT121/WDR35, IFT122, IFT139/TTC21B, IFT140, and IFT144/WDR19) often result in skeletal ciliopathies, including cranioectodermal dysplasia (CED). We here characterized the molecular and cellular defects of CED caused by compound heterozygous mutations in IFT144 [the missense variant IFT144(L710S) and the nonsense variant IFT144(R1103*)]. These two variants were distinct with regard to their interactions with other IFT-A subunits and with the IFT-B complex. When exogenously expressed in IFT144-knockout (KO) cells, IFT144(L710S) as well as IFT144(WT) rescued both moderately compromised ciliogenesis and the abnormal localization of ciliary proteins. As the homozygous IFT144(L710S) mutation was found to cause autosomal recessive retinitis pigmentosa, IFT144(L710S) is likely to be hypomorphic at the cellular level. In striking contrast, the exogenous expression of IFT144(R1103*) in IFT144-KO cells exacerbated the ciliogenesis defects. The expression of IFT144(R1103*) together with IFT144(WT) restored the abnormal phenotypes of IFT144-KO cells. However, the coexpression of IFT144(R1103*) with the hypomorphic IFT144(L710S) variant in IFT144-KO cells, which mimics the genotype of compound heterozygous CED patients, resulted in severe ciliogenesis defects. Taken together, these observations demonstrate that compound heterozygous mutations in IFT144 cause severe ciliary defects via a complicated mechanism, where one allele can cause severe ciliary defects when combined with a hypomorphic allele.

scholarly journals Chlamydomonas WDR92 in association with R2TP-like complex and multiple DNAAFs to regulate ciliary dynein preassembly

2018 ◽  
Vol 11 (9) ◽  
pp. 770-780 ◽  
Author(s):  
Guang Liu ◽  
Limei Wang ◽  
Junmin Pan
Keyword(s):  
Mass Spectrometry ◽  
Insertional Mutagenesis ◽  
The Other ◽  
Cytoplasmic Protein ◽  
Flagellar Motility ◽  
Heavy Chains ◽  
The Third ◽  
Axonemal Dynein ◽  
Dynein Arms ◽  
Dna Insertional Mutagenesis

Abstract The motility of cilia or eukaryotic flagella is powered by the axonemal dyneins, which are preassembled in the cytoplasm by proteins termed dynein arm assembly factors (DNAAFs) before being transported to and assembled on the ciliary axoneme. Here, we characterize the function of WDR92 in Chlamydomonas. Loss of WDR92, a cytoplasmic protein, in a mutant wdr92 generated by DNA insertional mutagenesis resulted in aflagellate cells or cells with stumpy or short flagella, disappearance of axonemal dynein arms, and diminishment of dynein arm heavy chains in the cytoplasm, suggesting that WDR92 is a DNAAF. Immunoprecipitation of WDR92 followed by mass spectrometry identified inner dynein arm heavy chains and multiple DNAAFs including RuvBL1, RPAP3, MOT48, ODA7, and DYX1C. The PIH1 domain-containing protein MOT48 formed a R2TP-like complex with RuvBL1/2 and RPAP3, while PF13, another PIH1 domain-containing protein with function in dynein preassembly, did not. Interestingly, the third PIH1 domain-containing protein TWI1 was not related to flagellar motility. WDR92 physically interacted with the R2TP-like complex and the other identified DNNAFs. Our data suggest that WDR92 functions in association with the HSP90 co-chaperone R2TP-like complex as well as linking other DNAAFs in dynein preassembly.

scholarly journals The DHC1b (DHC2) Isoform of Cytoplasmic Dynein Is Required for Flagellar Assembly

1999 ◽  
Vol 144 (3) ◽  
pp. 473-481 ◽  
Author(s):  
Gregory J. Pazour ◽  
Bethany L. Dickert ◽  
George B. Witman
Keyword(s):  
Molecular Motors ◽  
Cell Movement ◽  
Intraflagellar Transport ◽  
Cytoplasmic Dynein ◽  
Cdna Clones ◽  
Western Blots ◽  
Heavy Chains ◽  
Different Types ◽  
Flagellar Assembly ◽  
Soluble Fractions

Dyneins are microtubule-based molecular motors involved in many different types of cell movement. Most dynein heavy chains (DHCs) clearly group into cytoplasmic or axonemal isoforms. However, DHC1b has been enigmatic. To learn more about this isoform, we isolated Chlamydomonas cDNA clones encoding a portion of DHC1b, and used these clones to identify a Chlamydomonas cell line with a deletion mutation in DHC1b. The mutant grows normally and appears to have a normal Golgi apparatus, but has very short flagella. The deletion also results in a massive redistribution of raft subunits from a peri-basal body pool (Cole, D.G., D.R. Diener, A.L. Himelblau, P.L. Beech, J.C. Fuster, and J.L. Rosenbaum. 1998. J. Cell Biol. 141:993–1008) to the flagella. Rafts are particles that normally move up and down the flagella in a process known as intraflagellar transport (IFT) (Kozminski, K.G., K.A. Johnson, P. Forscher, and J.L. Rosenbaum. 1993. Proc. Natl. Acad. Sci. USA. 90:5519–5523), which is essential for assembly and maintenance of flagella. The redistribution of raft subunits apparently occurs due to a defect in the retrograde component of IFT, suggesting that DHC1b is the motor for retrograde IFT. Consistent with this, Western blots indicate that DHC1b is present in the flagellum, predominantly in the detergent- and ATP-soluble fractions. These results indicate that DHC1b is a cytoplasmic dynein essential for flagellar assembly, probably because it is the motor for retrograde IFT.

scholarly journals Chlamydomonas IFT70/CrDYF-1 Is a Core Component of IFT Particle Complex B and Is Required for Flagellar Assembly

2010 ◽  
Vol 21 (15) ◽  
pp. 2696-2706 ◽  
Author(s):  
Zhen-Chuan Fan ◽  
Robert H. Behal ◽  
Stefan Geimer ◽  
Zhaohui Wang ◽  
Shana M. Williamson ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Chlamydomonas Reinhardtii ◽  
Posttranslational Modification ◽  
Model Organism ◽  
Intraflagellar Transport ◽  
Apparent Size ◽  
Model Organisms ◽  
Core Component ◽  
B Subunit ◽  
Flagellar Assembly

DYF-1 is a highly conserved protein essential for ciliogenesis in several model organisms. In Caenorhabditis elegans, DYF-1 serves as an essential activator for an anterograde motor OSM-3 of intraflagellar transport (IFT), the ciliogenesis-required motility that mediates the transport of flagellar precursors and removal of turnover products. In zebrafish and Tetrahymena DYF-1 influences the cilia tubulin posttranslational modification and may have more ubiquitous function in ciliogenesis than OSM-3. Here we address how DYF-1 biochemically interacts with the IFT machinery by using the model organism Chlamydomonas reinhardtii, in which the anterograde IFT does not depend on OSM-3. Our results show that this protein is a stoichiometric component of the IFT particle complex B and interacts directly with complex B subunit IFT46. In concurrence with the established IFT protein nomenclature, DYF-1 is also named IFT70 after the apparent size of the protein. IFT70/CrDYF-1 is essential for the function of IFT in building the flagellum because the flagella of IFT70/CrDYF-1–depleted cells were greatly shortened. Together, these results demonstrate that IFT70/CrDYF-1 is a canonical subunit of IFT particle complex B and strongly support the hypothesis that the IFT machinery has species- and tissue-specific variations with functional ramifications.

scholarly journals Chlamydomonas Basal Bodies as Flagella Organizing Centers

Cells ◽  
2018 ◽  
Vol 7 (7) ◽  
pp. 79 ◽  
Author(s):  
Jenna Wingfield ◽  
Karl-Ferdinand Lechtreck
Keyword(s):  
Structure Function ◽  
Chlamydomonas Reinhardtii ◽  
Developmental Disorders ◽  
Intraflagellar Transport ◽  
Specific Protein ◽  
Basal Bodies ◽  
Unicellular Green Alga ◽  
Flagellar Assembly ◽  
Flagellar Axoneme

During ciliogenesis, centrioles convert to membrane-docked basal bodies, which initiate the formation of cilia/flagella and template the nine doublet microtubules of the flagellar axoneme. The discovery that many human diseases and developmental disorders result from defects in flagella has fueled a strong interest in the analysis of flagellar assembly. Here, we will review the structure, function, and development of basal bodies in the unicellular green alga Chlamydomonas reinhardtii, a widely used model for the analysis of basal bodies and flagella. Intraflagellar transport (IFT), a flagella-specific protein shuttle critical for ciliogenesis, was first described in C. reinhardtii. A focus of this review will be on the role of the basal bodies in organizing the IFT machinery.

scholarly journals The Distribution of eIF4E-Family Members across Insecta

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Gritta Tettweiler ◽  
Michelle Kowanda ◽  
Paul Lasko ◽  
Nahum Sonenberg ◽  
Greco Hernández
Keyword(s):  
Animal Species ◽  
Human Life ◽  
Model Organism ◽  
Animal Group ◽  
Eukaryotic Translation ◽  
Fundamental Process ◽  
Genes Encoding ◽  
Terrestrial Environments ◽  
Huge Impact ◽  
Striking Contrast

Insects are part of the earliest faunas that invaded terrestrial environments and are the first organisms that evolved controlled flight. Nowadays, insects are the most diverse animal group on the planet and comprise the majority of extant animal species described. Moreover, they have a huge impact in the biosphere as well as in all aspects of human life and economy; therefore understanding all aspects of insect biology is of great importance. In insects, as in all cells, translation is a fundamental process for gene expression. However, translation in insects has been mostly studied only in the model organismDrosophila melanogaster. We used all publicly available genomic sequences to investigate in insects the distribution of the genes encoding the cap-binding proteineIF4E, a protein that plays a crucial role in eukaryotic translation. We found that there is a diversity of multiple ortholog genes encoding eIF4E isoforms within the genusDrosophila. In striking contrast, insects outside this genus contain only a singleeIF4Egene, related toD. melanogastereIF4E-1. We also found that all insect species here analyzed contain only one Class II gene, termed4E-HP. We discuss the possible evolutionary causes originating the multiplicity ofeIF4Egenes within the genusDrosophila.

scholarly journals Updated Sequence Information and Proposed Nomenclature for blaTEM Genes and Their Promoters

2000 ◽  
Vol 44 (11) ◽  
pp. 3232-3234 ◽  
Author(s):  
V. Leflon-Guibout ◽  
B. Heym ◽  
M.-H. Nicolas-Chanoine
Keyword(s):  
Genetic Variability ◽  
Nucleotide Sequences ◽  
Sequence Information ◽  
Gene Nomenclature ◽  
Different Types ◽  
Genes Encoding

ABSTRACT The nucleotide sequences of 59 bla TEM genes encoding inhibitor-resistant TEM enzymes showed great genetic variability and were associated with different types of promoters. These findings led us to suggest an updatedbla TEM gene nomenclature based on the origin of the bla TEM gene (bla TEM-1A, bla TEM-1B,bla TEM-1C, bla TEM-1D,bla TEM-1E, andbla TEM-1F) and the promoter type.

A cilia-mediated environmental input induces solitary behaviour in Caenorhabditis elegans and Pristionchus pacificus nematodes

Nematology ◽  
2018 ◽  
Vol 20 (3) ◽  
pp. 201-209 ◽  
Author(s):  
Eduardo Moreno ◽  
Ralf J. Sommer
Keyword(s):  
Caenorhabditis Elegans ◽  
Social Behaviour ◽  
Intraflagellar Transport ◽  
Large Protein ◽  
Pristionchus Pacificus ◽  
C Elegans ◽  
The Social ◽  
Genes Encoding ◽  
Social Behaviours ◽  
Ciliated Neurons

Nematodes respond to a multitude of environmental cues. For example, the social behaviours clumping and bordering were described as a mechanism of hyperoxia avoidance in Caenorhabditis elegans and Pristionchus pacificus. A recent study in P. pacificus revealed a novel regulatory pathway that inhibits social behaviour in a response to an as yet unknown environmental cue. This environmental signal is recognised by ciliated neurons, as mutants defective in intraflagellar transport (IFT) proteins display social behaviours. The IFT machinery represents a large protein complex and many mutants in genes encoding IFT proteins are available in C. elegans. However, social phenotypes in C. elegans IFT mutants have never been reported. Here, we examined 15 previously isolated C. elegans IFT mutants and found that most of them showed strong social behaviour. These findings indicate conservation in the inhibitory mechanism of social behaviour between P. pacificus and C. elegans.

scholarly journals The kinesin superfamily protein KIF17: one protein with many functions

2012 ◽  
Vol 3 (3) ◽  
pp. 267-282 ◽  
Author(s):  
Margaret T.T. Wong-Riley ◽  
Joseph C. Besharse
Keyword(s):  
Molecular Motors ◽  
Coiled Coil ◽  
Intraflagellar Transport ◽  
Brain Regions ◽  
Sensory Cells ◽  
Tail Domain ◽  
Nuclear Respiratory Factor ◽  
Nuclear Respiratory Factor 1 ◽  
Chemosensory Perception ◽  
Dependent Transport

AbstractKinesins are ATP-dependent molecular motors that carry cargos along microtubules, generally in an anterograde direction. They are classified into 14 distinct families with varying structural and functional characteristics. KIF17 is a member of the kinesin-2 family that is plus end-directed. It is a homodimer with a pair of head motor domains that bind microtubules, a coiled-coil stalk, and a tail domain that binds cargos. In neurons, KIF17 transports N-methyl-D-aspartate receptor NR2B subunit, kainate receptor GluR5, and potassium Kv4.2 channels from cell bodies exclusively to dendrites. These cargos are necessary for synaptic transmission, learning, memory and other functions. KIF17’s interaction with nuclear RNS export factor 2 (NXF2) enables the transport of mRNA bidirectionally in dendrites. KIF17 or its homolog osmotic avoidance abnormal protein 3 (OSM-3) also mediates intraflagellar transport of cargos to the distal tips of flagella or cilia, thereby aiding in ciliogenesis. In many invertebrate and vertebrate sensory cells, KIF17 delivers cargos that contribute to chemosensory perception and signal transduction. In vertebrate photoreceptors, KIF17 is necessary for outer segment development and disc morphogenesis. In the testis, KIF17 (KIF17b) mediates microtubule-independent delivery of an activator of cAMP-responsive element modulator (ACT) from the nucleus to the cytoplasm and microtubule-dependent transport of Spatial-ε, both are presumably involved in spermatogenesis. KIF17 is also implicated in epithelial polarity and morphogenesis, placental transport and development, and the development of specific brain regions. The transcriptional regulation of Kif17 has recently been found to be mediated by nuclear respiratory factor 1 (NRF-1), which also regulates NR2B as well as energy metabolism in neurons. Dysfunctions of KIF17 are linked to a number of pathologies.

scholarly journals How signals of calcium ions initiate the beats of cilia and flagella

2019 ◽  
Author(s):  
M. V. Satarić ◽  
T. Nemeš ◽  
D. Sekulić ◽  
J. A. Tuszynski
Keyword(s):  
Atp Hydrolysis ◽  
Cellular Motility ◽  
Cell Organelles ◽  
Ciliary Movement ◽  
Ciliary Function ◽  
Dynein Motor ◽  
Combined Action ◽  
Axonemal Dynein ◽  
Cilia And Flagella

ABSTRACTCilia and flagella are cell organelles serving basic roles in cellular motility. Ciliary movement is performed by a sweeping-like repeated bending motion, which gives rise to a self-propagating “ciliary beat”. The hallmark structure in cilia is the axoneme, a stable architecture of microtubule doublets. The motion of axoneme is powered by the axonemal dynein motor family powered by ATP hydrolysis. It is still unclear how the organized beat of cilium and flagella emerges from the combined action of hundreds of dynein molecules. It has been hypothesized that such coordination is mediated by mechanical stress due to transverse, radial or sliding deformations. The beating asymmetry is crucial for airway ciliary function and it requires tubulin glutamination a unique posttranslational modification of C-termini of constituent microtubules that is highly abundant in cilia and flagella. The exact role of tubulin glutamination in ciliary or flagellar function is still unclear. Here we examine the role of calcium (Ca2+) ions based on the experimental evidences that the flagellar asymmetry can be increased due to the entry of extracellular Ca2+through, for example, nimodipine-sensitive pathway located in the flagella. We propose a new scenario based on the polyelectrolyte properties of cellular microtubules (MTs) such that dynamic influx of Ca2+ions provides the initiation and synchronization of dynein sliding along microtubules. We also point out the possible interplay between tubulin polyglutaminated C-termini and localized pulses of Ca2+ions along microtubules.

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