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Combined Extracellular Matrix Cross-linking Activity of the Peroxidase MLT-7 and the Dual Oxidase BLI-3 Is Critical for Post-embryonic Viability in Caenorhabditis elegans
- Source :
- Journal of Biological Chemistry. 284:17549-17563
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- The nematode cuticle is a protective collagenous extracellular matrix that is modified, cross-linked, and processed by a number of key enzymes. This Ecdysozoan-specific structure is synthesized repeatedly and allows growth and development in a linked degradative and biosynthetic process known as molting. A targeted RNA interference screen using a cuticle collagen marker has been employed to identify components of the cuticle biosynthetic pathway. We have characterized an essential peroxidase, MoLT-7 (MLT-7), that is responsible for proper cuticle molting and re-synthesis. MLT-7 is an active, inhibitable peroxidase that is expressed in the cuticle-synthesizing hypodermis coincident with each larval molt. mlt-7 mutants show a range of body morphology defects, most notably molt, dumpy, and early larval stage arrest phenotypes that can all be complemented with a wild type copy of mlt-7. The cuticles of these mutants lacks di-tyrosine cross-links, becomes permeable to dye and accessible to tyrosine iodination, and have aberrant collagen protein expression patterns. Overexpression of MLT-7 causes mutant phenotypes further supporting its proposed enzymatic role. In combination with BLI-3, an H2O2-generating NADPH dual oxidase, MLT-7 is essential for post-embryonic development. Disruption of mlt-7, and particularly bli-3, via RNA interference also causes dramatic changes to the in vivo cross-linking patterns of the cuticle collagens DPY-13 and COL-12. This points toward a functionally cooperative relationship for these two hypodermally expressed proteins that is essential for collagen cross-linking and proper extracellular matrix formation.
- Subjects :
- Male
Embryo, Nonmammalian
Cuticle
Molecular Sequence Data
Mutant
Glycobiology and Extracellular Matrices
Biochemistry
Animals, Genetically Modified
Extracellular matrix
Gene expression
Animals
Amino Acid Sequence
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Molecular Biology
Sequence Homology, Amino Acid
biology
Wild type
Gene Expression Regulation, Developmental
NADPH Oxidases
Cell Biology
biology.organism_classification
Recombinant Proteins
Extracellular Matrix
Cross-Linking Reagents
Phenotype
Peroxidases
Biosynthetic process
Mutation
biology.protein
Female
RNA Interference
Collagen
Peroxidase
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 284
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....fddf6e2921f07585927e313398abcf37