Winter, A. D., Eschenlauer, S. C. P., McCormack, G. and Page, A. P. (2007) Loss of secretory pathway FK506-binding proteins results in cold-sensitive lethality in caenorhabditis elegans. Journal of Biological Chemistry, 282(17), pp. 12813-12821. (doi: 10.1074/jbc.M700274200)
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Publisher's URL: http://dx.doi.org/10.1074/jbc.M700274200
Abstract
The FK506-binding proteins (FKBs) represent ubiquitous enzymes that catalyse the rate-limiting peptidyl prolyl cis-trans isomerization step in protein folding. The nematode <i>Caenorhabditis elegans</i> has eight FKBs, three of which (FKB-3, -4 and -5) have dual peptidyl prolyl <i>cis-trans</i> 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-synthesising 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 <i>fkb-4/-5</i> double deletion mutants were found to arrest at 12°C, but developed normally at 15-25°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 <i>fkb-4 or fkb-5</i>. 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Page, Professor Tony and McCormack, Ms Gillian and Winter, Dr Alan |
| Authors: | Winter, A. D., Eschenlauer, S. C. P., McCormack, G., and Page, A. P. |
| Subjects: | Q Science > QH Natural history > QH345 Biochemistry Q Science > QH Natural history > QH426 Genetics |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Group: | Page Group |
| Journal Name: | Journal of Biological Chemistry |
| Journal Abbr.: | J Biol Chem. |
| Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0021-9258 |
| ISSN (Online): | 1083-351X |
| Published Online: | 05 March 2007 |
| Copyright Holders: | Copyright © 2007 American Society for Biochemistry and Molecular Biology |
| First Published: | First published in Journal of Biological Chemistry 282(17):12813-12821 |
| Related URLs: |
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