Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture

Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture

Bromine is ubiquitously present in animals as ionic bromide (Br(-)) yet has no known essential function. Herein, we demonstrate that Br(-) is a required cofactor for peroxidasin-catalyzed formation of sulfilimine crosslinks, a posttranslational modification essential for tissue development and archi...

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Bibliographic Details
Published in:Cell Vol. 157; no. 6; pp. 1380 - 1392
Main Authors: McCall, A Scott, Cummings, Christopher F, Bhave, Gautam, Vanacore, Roberto, Page-McCaw, Andrea, Hudson, Billy G
Format: Journal Article
Language:English
Published: United States 05-06-2014
Subjects:
Animals
Basement Membrane - metabolism
Basement Membrane - ultrastructure
Bromine - deficiency
Bromine - metabolism
Cell Line
Collagen - metabolism
Drosophila - growth & development
Drosophila - metabolism
Extracellular Matrix Proteins - genetics
Extracellular Matrix Proteins - metabolism
Humans
Imines - metabolism
Larva - ultrastructure
Mice
Peroxidase - genetics
Peroxidase - metabolism
Peroxidasin
Trace Elements - metabolism
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Summary:Bromine is ubiquitously present in animals as ionic bromide (Br(-)) yet has no known essential function. Herein, we demonstrate that Br(-) is a required cofactor for peroxidasin-catalyzed formation of sulfilimine crosslinks, a posttranslational modification essential for tissue development and architecture found within the collagen IV scaffold of basement membranes (BMs). Bromide, converted to hypobromous acid, forms a bromosulfonium-ion intermediate that energetically selects for sulfilimine formation. Dietary Br deficiency is lethal in Drosophila, whereas Br replenishment restores viability, demonstrating its physiologic requirement. Importantly, Br-deficient flies phenocopy the developmental and BM defects observed in peroxidasin mutants and indicate a functional connection between Br(-), collagen IV, and peroxidasin. We establish that Br(-) is required for sulfilimine formation within collagen IV, an event critical for BM assembly and tissue development. Thus, bromine is an essential trace element for all animals, and its deficiency may be relevant to BM alterations observed in nutritional and smoking-related disease. PAPERFLICK:
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These authors contributed equally to this work.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2014.05.009