Affiliation:
1. Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India
2. Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India
3. Lead contact
Abstract
AbstractCollagen-enriched cuticle forms the outermost layer of skin in nematode Caenorhabditis elegans. The nematode’s genome encodes 177 collagens, but little is known about their role in maintaining the structure or barrier function of the cuticle. In this study, we found six permeability determining (PD) collagens. Loss of any of these PD collagens—DPY-2, DPY-3, DPY-7, DPY-8, DPY-9, and DPY-10—led to enhanced susceptibility of nematodes to paraquat (PQ) and antihelminthic drugs- levamisole and ivermectin. Upon exposure to PQ, PD collagen mutants accumulated more PQ and incurred more damage and death despite the robust activation of antioxidant machinery. We find that BLMP-1, a zinc finger transcription factor, maintains the barrier function of the cuticle by regulating the expression of PD collagens. We show that the permeability barrier maintained by PD collagens acts in parallel to FOXO transcription factor DAF-16 to enhance survival of insulin-like receptor mutant, daf-2. In all, this study shows that PD collagens regulate cuticle permeability by maintaining the structure of C. elegans cuticle and thus provide protection against exogenous toxins.
Funder
Wellcome Trust
DBT India Alliance Intermediate Fellowship
DBT-IISc Partnership Program
DST-FIST
Publisher
Oxford University Press (OUP)
Cited by
42 articles.
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