PUBLICATION

Identification of unique α4 chain structure and conserved anti-angiogenic activity of α3NC1 type IV collagen in zebrafish

Authors
LeBleu, V.S., Dai, J., Tsutakawa, S., MacDonald, B.A., Alge, J.L., Sund, M., Xie, L., Sugimoto, H., Tainer, J., Zon, L.I., Kalluri, R.
ID
ZDB-PUB-230402-50
Date
2023
Source
Developmental Dynamics : an official publication of the American Association of Anatomists   252(7): 1046-1060 (Journal)
Registered Authors
Zon, Leonard I.
Keywords
Tumstatin, angiogenesis, basement membrane, collagen IV, zebrafish
MeSH Terms
  • Animals
  • Basement Membrane/metabolism
  • Collagen Type IV*/genetics
  • Endothelial Cells
  • Humans
  • Protein Subunits/analysis
  • Protein Subunits/metabolism
  • Zebrafish*
PubMed
37002899 Full text @ Dev. Dyn.
Abstract
Type IV collagen is an abundant component of basement membranes in all multicellular species and is essential for the extracellular scaffold supporting tissue architecture and function. Lower organisms typically have two type IV collagen genes, encoding α1 and α2 chains, in contrast with the six genes in humans, encoding α1 to α6 chains. The α chains assemble into trimeric protomers, the building blocks of the type IV collagen network. The detailed evolutionary conservation of type IV collagen network remains to be studied.
We report on the molecular evolution of type IV collagen genes. The zebrafish α4 non-collagenous (NC1) domain, in contrast with its human ortholog, contains an additional cysteine residue and lacks the M93 and K211 residues involved in sulfilimine bond formation between adjacent protomers. This may alter α4 chain interactions with other α chains, as supported by temporal and anatomic expression patterns of collagen IV chains during zebrafish development. Despite the divergence between zebrafish and human α3 NC1 domain (endogenous angiogenesis inhibitor, Tumstatin), the zebrafish α3 NC1 domain exhibits conserved anti-angiogenic activity in human endothelial cells.
Our work supports type IV collagen is largely conserved between zebrafish and humans, with a possible difference involving the α4 chain. This article is protected by copyright. All rights reserved.
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