Loss of Secretory Pathway FK506-binding Proteins Results in Cold-sensitive Lethality and Associate Extracellular Matrix Defects in the Nematode Caenorhabditis elegans
| Autor: | Alan D. Winter, Gillian McCormack, Antony P. Page, Sylvain C.P. Eschenlauer |
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| Rok vydání: | 2007 |
| Předmět: |
Signal peptide
Transgene Molting Biology Cell morphology Biochemistry Animals Genetically Modified Tacrolimus Binding Proteins Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Secretory pathway chemistry.chemical_classification Wild type ER retention Cell Biology Peptidylprolyl Isomerase Molecular biology Extracellular Matrix Cell biology Cold Temperature Enzyme chemistry Collagen Gene Deletion Biogenesis |
| Zdroj: | Journal of Biological Chemistry. 282:12813-12821 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m700274200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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