The Conserved Proteins CHE-12 and DYF-11 Are Required for Sensory Cilium Function in <i>Caenorhabditis elegans</i>

Bacaj, Taulant; Lu, Yun; Shaham, Shai

doi:10.1534/genetics.107.082453

Cited by 44 publications

(61 citation statements)

References 67 publications

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“…Ciliary genes that are controlled by DAF-19 are also expressed at a significantly lower level in daf-19 mutant worms compared to wild type (Bacaj et al, 2008; Blacque et al, 2005; Chen et al, 2006; Efimenko et al, 2005; Mukhopadhyay et al, 2008; Swoboda et al, 2000; Winkelbauer et al, 2005). Thus, subjecting worms that contain mutations in any of our candidate genes to a variety of these phenotypic or regulatory assays will likely reveal genes with cilia-specific functions.…”

Section: Resultsmentioning

confidence: 96%

Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport

Phirke

Efimenko

Mohan

et al. 2011

Developmental Biology

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Cilia are ubiquitous cell surface projections that mediate various sensory- and motility-based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. To identify new components required for cilium biogenesis and function, we sought to further define and validate the transcriptional targets of DAF-19, the ciliogenic C. elegans RFX transcription factor. Transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using embryos staged to when the cell types developing cilia in the worm, the ciliated sensory neurons (CSNs), still differentiate. Comparisons between the two populations revealed 881 differentially regulated genes with greater than a 1.5-fold increase or decrease in expression. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional GFP fusions revealed CSN-specific expression patterns for 11 of 14 candidate genes. We show that two uncharacterized candidate genes, termed dyf-17 and dyf-18 because their corresponding mutants display dye-filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the base of cilia and is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK7/CCRK/LF2p-related serine/threonine kinase that is necessary for the proper function of intraflagellar transport, a process critical for cilium biogenesis. Together, our microarray study identifies targets of the evolutionarily conserved RFX transcription factor, DAF-19, providing a rich dataset from which to uncover—in addition to DYF-17 and DYF-18—cellular components important for cilium formation and function.

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Section: Resultsmentioning

confidence: 96%

Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport

Phirke

Efimenko

Mohan

et al. 2011

Developmental Biology

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“…In C. elegans amphid sheath cells are required for the elongation of the dendrites of sensory neurons and for the establishment and remodeling of their receptive sensory endings, the cilia (Bacaj et al, 2008a; Yoshimura et al, 2008; Procko et al, 2011). We thus wondered whether DELM-1 and DELM-2 were needed for neuronal structural development or integrity.…”

Section: Resultsmentioning

confidence: 99%

Two Novel DEG/ENaC Channel Subunits Expressed in Glia Are Needed for Nose-Touch Sensitivity inCaenorhabditis elegans

et al. 2013

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Summary Neuronal DEG/ENaC Na+ channels have been implicated in touch sensation. For example, MEC-4 is expressed in touch neurons in C. elegans and mediates gentle touch response. Similarly, homologous mammalian ASIC2 and ASIC3 are expressed in sensory neurons and produce touch phenotypes when knocked out in mice. Here, we show that novel DEG/ENaC subunits DELM-1 and DELM-2 are expressed in glia associated with touch neurons in C. elegans and that their knock-out causes defects in mechanosensory behaviors related to nose touch and foraging, which are mediated by OLQ and IL1 sensory neurons. Cell-specific rescue supports that DELM-1 and DELM-2 are required cell-autonomously in glia to orchestrate mechanosensory behaviors. Electron microscopy reveals that in delm-1 knockouts, OLQ and IL1 sensory neurons and associated glia are structurally normal. Furthermore, we show that knockout of DELM-1 and DELM-2 does not disrupt the expression or cellular localization of TRPA-1, a TRP channel needed in OLQ and IL1 neurons for touch behaviors. Rather, rescue of the delm-1 nose-touch insensitive phenotype by expression of a K+ channel in socket glia and of a cationic channel in OLQ neurons suggests that DELM channels set basal neuronal excitability. Taken together, our data show that DELM-1 and DELM-2 are expressed in glia associated with touch neurons where they are not needed for neuronal structural integrity or cellular distribution of neuronal sensory channels, but rather for their function.

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“…MIP-T3 is a ciliary protein required for ciliogenesis and intraflagellar transport (18)(19)(20)(21). Particularly, MIP-T3 has been suggested to be a new component of intraflagellar transport subcomplex B (71).…”

Section: Discussionmentioning

confidence: 99%

“…MIP-T3 has been found to localize to the cytoplasm, the primary cilium, and the centrosome (17)(18)(19)(20)(21). Although MIP-T3 is a component of the intraflagellar transport subcomplex B that plays an important role in primary cilium formation (18)(19)(20)(21)(22), nonciliary functions of MIP-T3, exemplified by the recruitment of schizophrenia susceptibility factor DISC1 to the centrosome and an inhibitory role in IL-13 signaling, have also been implicated (23)(24)(25). The biologic relevance of the interaction between TRAF3 and MIP-T3 remains elusive.…”

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confidence: 99%

MIP-T3 Is a Negative Regulator of Innate Type I IFN Response

Kok

et al. 2011

The Journal of Immunology

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TNFR-associated factor (TRAF) 3 is an important adaptor that transmits upstream activation signals to protein kinases that phosphorylate transcription factors to induce the production of type I IFNs, the important effectors in innate antiviral immune response. MIP-T3 interacts specifically with TRAF3, but its function in innate IFN response remains unclear. In this study, we demonstrated a negative regulatory role of MIP-T3 in type I IFN production. Overexpression of MIP-T3 inhibited RIG-I-, MDA5-, VISA-, TBK1-, and IKKε-induced transcriptional activity mediated by IFN-stimulated response elements and IFN-β promoter. MIP-T3 interacted with TRAF3 and perturbed in a dose-dependent manner the formation of functional complexes of TRAF3 with VISA, TBK1, IKKε, and IFN regulatory factor 3. Consistent with this finding, retinoic acid-inducible gene I- and TBK1-induced phosphorylation of IFN regulatory factor 3 was significantly diminished when MIP-T3 was overexpressed. Depletion of MIP-T3 facilitated Sendai virus-induced activation of IFN production and attenuated the replication of vesicular stomatitis virus. In addition, MIP-T3 was found to be dissociated from TRAF3 during the course of Sendai virus infection. Our findings suggest that MIP-T3 functions as a negative regulator of innate IFN response by preventing TRAF3 from forming protein complexes with critical downstream transducers and effectors.

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The Conserved Proteins CHE-12 and DYF-11 Are Required for Sensory Cilium Function in Caenorhabditis elegans

Cited by 44 publications

References 67 publications

Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport

Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport

Two Novel DEG/ENaC Channel Subunits Expressed in Glia Are Needed for Nose-Touch Sensitivity inCaenorhabditis elegans

MIP-T3 Is a Negative Regulator of Innate Type I IFN Response

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