Peroxidasin-like protein: a novel peroxidase homologue in the human heart

Bandyopadhyay

et al. 2015

Molecules and Cells

The Caenorhabditis elegans peroxidasins, PXN-1 and PXN-2, are extracellular peroxidases; pxn-2 is involved in muscle-epidermal attachment during embryonic morphogenesis and in specific axon guidance. Here we investigate potential roles of the other homologue of peroxidasin, pxn-1, in C. elegans. A pxn-1 deletion mutant showed high lethality under heat-stress conditions. Using a transcriptional GFP reporter, pxn-1 expression was observed in various tissues including neurons, muscles, and hypodermis. A translational fusion showed that PXN-1::GFP was secreted and localized in extracellular matrix, particularly along body wall muscles and pharyngeal muscles. Various neuronal developmental defects were observed in pxn-1 mutants and in pxn-1 over-expressing animals, including handedness, branching, breakage, tangling, and defasciculation. These results suggest that pxn-1, like other peroxidasins, plays an important role throughout development.

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Role for Peroxidasin PXN-1 in Aspects of C. elegans Development

Bandyopadhyay

et al. 2015

Molecules and Cells

Free Radical Biology and Medicine

“…A peroxidasin-like protein (PXDNL) was recently identified in humans (3), however this protein lacks measurable peroxidase activity. Animal heme peroxidases (MPO, EPX and LPO) serve in the first line of host defense, while TPO has a crucial role in thyroid hormone synthesis.…”

Section: Introductionmentioning

confidence: 99%

Structure–function analysis of peroxidasin provides insight into the mechanism of collagen IV crosslinking

Lázár

Péterfi

Sirokmány

et al. 2015

Self Cite

Basement membranes provide structural support and convey regulatory signals to cells in diverse tissues. Assembly of collagen IV into a sheet-like network is a fundamental mechanism during the formation of basement membranes. Peroxidasin (PXDN) was recently described to catalyze crosslinking of collagen IV through the formation of sulfilimine bonds.Despite the significance of this pathway in tissue genesis, our understanding of PXDN function is far from complete. In this work we demonstrate that collagen IV crosslinking is a physiological function of mammalian PXDN. Moreover, we carried out structure-function analysis of PXDN to get a better insight into its role in collagen IV synthesis. We identify conserved cysteines in PXDN which mediate the oligomerization of the protein into a trimeric complex. We also demonstrate that oligomerization is not an absolute requirement for enzymatic activity but optimal collagen IV coupling is only catalyzed by the PXDN trimers.Localization experiments of different PXDN mutants in two different cell models revealed that PXDN oligomers, but not monomers, adhere on cell-surface in "hot spots", which represent previously unknown locations of collagen IV crosslinking.

“…PXDN, a member of the larger peroxidase gene family, is an adhesion molecule involved in ECM formation (Peterfi et al 2014;Tauber et al 2010). It is one of the target genes of miR-29a.…”

Section: Relationship Between Genes' Expression and Survival In Primamentioning

confidence: 99%

A gene expression signature for defining aggressive phenotype and prognosis in intermediate-risk acute myeloid leukemia

Deng

2016

Preprint