Bromine Is an Essential Trace Element for Assembly of Collagen IV Scaffolds in Tissue Development and Architecture
Working with Billy Hudson's lab in the department of medicine, the Page-McCaw lab determined that the element bromine is required for crosslinking basement membrane, the extracellular matrix underlying all epithelial tissues. Without bromine, the basement membrane is weakened and fruitflies cannot survive. As this basement-membrane crosslink is highly conserved throughout the animal kingdom, this study establishes bromine as the 28th essential element. -APM
Cell. 2014 Jun 5;157(6):1380-92. doi: 10.1016/j.cell.2014.05.009.
Bromine Is an Essential Trace Element for Assembly of Collagen IV Scaffolds in Tissue Development and Architecture.
McCall AS1, Cummings CF2, Bhave G3, Vanacore R4, Page-McCaw A5, Hudson BG6.
Abstract
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:
Copyright © 2014 Elsevier Inc. All rights reserved.
PMID: 24906154 [PubMed – in process]