論文 - 詳細
| RRC ID | 3644 |
|---|---|
| 著者 | Winter AD, Eschenlauer SC, McCormack G, Page AP. |
| タイトル | Loss of secretory pathway FK506-binding proteins results in cold-sensitive lethality and associate extracellular matrix defects in the nematode Caenorhabditis elegans. |
| ジャーナル | J Biol Chem |
| Abstract |
The FK506-binding proteins (FKBs) represent ubiquitous enzymes that catalyze the rate-limiting peptidyl prolyl cis-trans isomerization step in protein folding. The nematode Caenorhabditis elegans has eight FKBs, three of which (FKB-3, -4, and -5) have dual peptidyl prolyl cis-trans isomerase (PPIase) domains, signal peptides and ER retention signals. PPIase activity has been detected for recombinant FKB-3. Both FKB-3 and -5 are expressed in the exoskeleton-synthesizing hypodermis with transcript peaks that correspond to the molting and collagen synthesis cycles. FKB-4 is expressed at a low level throughout development. No phenotypes were observed in deletion mutants in each of the secretory pathway FKBs. Combined triple and fkb-4, -5 double deletion mutants were however found to arrest at 12 degrees C, but developed normally at 15-25 degrees C. This cold-sensitive larval lethal effect was not maternally derived, occurred during embryogenesis, and could be rescued following the transgenic introduction of a wild type copy of either fkb-4 or fkb-5. The temperature-sensitive defects also affected molting, cuticle collagen expression, hypodermal seam cell morphology, and the structural integrity of the cuticular extracellular matrix. This study establishes that the secretory pathway FK506-binding PPIase enzymes are essential for normal nematode development, collagen biogenesis, and the formation of an intact exoskeleton under adverse physiological conditions. |
| 巻・号 | 282(17) |
| ページ | 12813-21 |
| 公開日 | 2007-4-27 |
| DOI | 10.1074/jbc.M700274200 |
| PII | S0021-9258(18)95057-X |
| PMID | 17339317 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cold Temperature Collagen / metabolism* Extracellular Matrix / metabolism* Extracellular Matrix / pathology Gene Deletion Molting / genetics Peptidylprolyl Isomerase / deficiency* Tacrolimus Binding Proteins / deficiency* |
| IF | 4.238 |
| 引用数 | 11 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm348 tm475 |