論文 - 詳細
| RRC ID | 4256 |
|---|---|
| 著者 | Li C, Inglis PN, Leitch CC, Efimenko E, Zaghloul NA, Mok CA, Davis EE, Bialas NJ, Healey MP, Héon E, Zhen M, Swoboda P, Katsanis N, Leroux MR. |
| タイトル | An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes. |
| ジャーナル | PLoS Genet |
| Abstract |
MIP-T3 is a human protein found previously to associate with microtubules and the kinesin-interacting neuronal protein DISC1 (Disrupted-in-Schizophrenia 1), but whose cellular function(s) remains unknown. Here we demonstrate that the C. elegans MIP-T3 ortholog DYF-11 is an intraflagellar transport (IFT) protein that plays a critical role in assembling functional kinesin motor-IFT particle complexes. We have cloned a loss of function dyf-11 mutant in which several key components of the IFT machinery, including Kinesin-II, as well as IFT subcomplex A and B proteins, fail to enter ciliary axonemes and/or mislocalize, resulting in compromised ciliary structures and sensory functions, and abnormal lipid accumulation. Analyses in different mutant backgrounds further suggest that DYF-11 functions as a novel component of IFT subcomplex B. Consistent with an evolutionarily conserved cilia-associated role, mammalian MIP-T3 localizes to basal bodies and cilia, and zebrafish mipt3 functions synergistically with the Bardet-Biedl syndrome protein Bbs4 to ensure proper gastrulation, a key cilium- and basal body-dependent developmental process. Our findings therefore implicate MIP-T3 in a previously unknown but critical role in cilium biogenesis and further highlight the emerging role of this organelle in vertebrate development. |
| 巻・号 | 4(3) |
| ページ | e1000044 |
| 公開日 | 2008-3-28 |
| DOI | 10.1371/journal.pgen.1000044 |
| PMID | 18369462 |
| PMC | PMC2268012 |
| MeSH | Animals Animals, Genetically Modified Base Sequence Biological Transport, Active Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cilia / physiology DNA Primers / genetics DNA, Helminth / genetics Flagella / physiology* Genes, Helminth Humans Intracellular Signaling Peptides and Proteins / chemistry Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / physiology* Microtubule-Associated Proteins / chemistry Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / physiology Morphogenesis Multiprotein Complexes Mutation Neurons, Afferent / physiology Phenotype Signal Transduction |
| IF | 5.175 |
| 引用数 | 47 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 線虫 | tm324 |