PUBLICATION
Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms
- Authors
- Umana-Diaz, C., Pichol-Thievend, C., Marchand, M.F., Atlas, Y., Salza, R., Malbouyres, M., Barret, A., Teillon, J., Ardidie-Robouant, C., Ruggiero, F., Monnot, C., Girard, P., Guilluy, C., Ricard-Blum, S., Germain, S., Muller, L.
- ID
- ZDB-PUB-210805-9
- Date
- 2020
- Source
- Matrix biology : journal of the International Society for Matrix Biology 88: 33-52 (Journal)
- Registered Authors
- Ruggiero, Florence
- Keywords
- Angiogenesis, ECM organization, Lysyl oxidase, Microenvironment remodeling, Vascular basement membrane
- MeSH Terms
-
- Amino Acid Oxidoreductases/chemistry*
- Amino Acid Oxidoreductases/genetics
- Amino Acid Oxidoreductases/metabolism*
- Animals
- Binding Sites
- Cell Line
- Collagen Type IV/metabolism
- Dermis/cytology
- Dermis/metabolism
- Extracellular Matrix/metabolism*
- Fibroblasts/cytology
- Fibroblasts/metabolism
- Fibronectins/metabolism
- Human Umbilical Vein Endothelial Cells
- Humans
- Mutagenesis, Site-Directed
- Neovascularization, Physiologic
- Protein Domains
- Zebrafish
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 31759052 Full text @ Matrix Biol.
Citation
Umana-Diaz, C., Pichol-Thievend, C., Marchand, M.F., Atlas, Y., Salza, R., Malbouyres, M., Barret, A., Teillon, J., Ardidie-Robouant, C., Ruggiero, F., Monnot, C., Girard, P., Guilluy, C., Ricard-Blum, S., Germain, S., Muller, L. (2020) Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms. Matrix biology : journal of the International Society for Matrix Biology. 88:33-52.
Abstract
Lysyl oxidases are major actors of microenvironment and extracellular matrix (ECM) remodeling. These cross-linking enzymes are thus involved in many aspects of physiopathology, including tumor progression, fibrosis and cardiovascular diseases. We have already shown that Lysyl Oxidase-Like 2 (LOXL2) regulates collagen IV deposition by endothelial cells and angiogenesis. We here provide evidence that LOXL2 also affects deposition of other ECM components, including fibronectin, thus altering structural and mechanical properties of the matrix generated by endothelial cells. LOXL2 interacts intracellularly and directly with collagen IV and fibronectin before incorporation into ECM fibrillar structures upon exocytosis, as demonstrated by TIRF time-lapse microscopy. Furthermore, surface plasmon resonance experiments using recombinant scavenger receptor cysteine-rich (SRCR) domains truncated for the catalytic domain demonstrated their direct binding to collagen IV. We thus used directed mutagenesis to investigate the role of LOXL2 catalytic domain. Neither enzyme activity nor catalytic domain were necessary for collagen IV deposition and angiogenesis, whereas the SRCR domains were effective for these processes. Finally, surface coating with recombinant SRCR domains restored deposition of collagen IV by LOXL2-depleted cells. We thus propose that LOXL2 SRCR domains orchestrate scaffolding of the vascular basement membrane and angiogenesis through interactions with collagen IV and fibronectin, independently of the enzymatic cross-linking activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping