Lysyl oxidase like-2 crosslinks collagen IV of glomerular basement membrane
The 7S dodecamer is recognized as an important structural crosslinking domain of collagen IV networks that provide mechanical stability to basement membranes, a specialized form of extracellular matrix essential for the development and maintenance of tissue architecture. Although the 7S dodecamer is...
| Autor Principal: | Añazco-Oyarzún, Carolina |
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| Otros Autores: | López-Jiménez, Alberto J., Rafi, Mohamed, Vega-Montoto, Lorenzo, Zhang, Ming-Zhi, Hudson, Billy G., Vanacore, Roberto M. |
| Formato: | Artículo |
| Idioma: | English |
| Publicado: |
2017
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| Materias: | |
| Acceso en línea: |
http://repositorio.ucm.cl:8080/handle/ucm/684 |
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| Sumario: |
The 7S dodecamer is recognized as an important structural crosslinking domain of collagen IV networks that provide mechanical stability to basement membranes, a specialized form of extracellular matrix essential for the development and maintenance of tissue architecture. Although the 7S dodecamer is stabilized by covalent crosslinking, the molecular mechanism by which such crosslinks are formed has not been revealed. Here we aimed to identify the enzyme(s) that crosslinks the 7S dodecamer and characterize its expression in the kidney glomerulus. Pharmacological inhibition of candidate ECM enzymes revealed that lysyl oxidase activity is required for crosslinking of 7S polypeptides. Among all lysyl oxidase family members, LOXL2 was identified as the isoform crosslinking collagen IV in mouse embryonal PFHR-9 cells. Biochemical analyses revealed that LOXL2 readily promoted the formation of lysyl-derived crosslinks in the 7S dodecamer, but not in the NC1 domain. We also established that LOXL2 is the main lysyl oxidase family member present in the glomerular ECM. Taking together, we demonstrate that LOXL2 is a novel component of the molecular machinery that forms crosslinked collagen IV networks, which are essential for glomerular basement membrane stability and molecular ultrafiltration function. |
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