November 21, 2016

Building the basement membrane

Vanderbilt researchers have discovered steps in the regulation of a key enzyme that builds the basement membrane, a structure that undergirds nearly all animal tissues.

Work by Billy Hudson, Ph.D., and colleagues have helped establish the critical role that the enzyme peroxidasin plays in the development of tissues throughout the Animal Kingdom.

Peroxidasin catalyzes the formation of the sulfilimine crosslinks between collagen IV molecules, a major constituent of the basement membrane. The basement membrane, in turn, undergirds cell layers and reinforces the structural integrity of nearly all animal tissues.

Little is known, however, about what regulates the activity of this essential enzyme.

Now, in the Journal of Biological Chemistry, Selen Colon and Gautam Bhave, M.D., Ph.D., report that another enzyme family, the pro-protein convertases, cleaves peroxidasin in a way that enhances its catalytic activity and promotes the formation of sulfilimine crosslinks.

“Processing” by pro-protein convertases is a widespread form of enzyme regulation. In this case, cleavage of peroxidasin produces a powerful oxidant, hydrobromous acid. More study is needed to determine how the oxidant is directed at collagen IV to catalyze sulfilimine crosslink formation, while minimizing collateral damage.

This research was supported by a grant from the National Institutes of Health (DK097306), a Burroughs Wellcome Fund Career Award for Medical Scientists, and developmental funds from the Vanderbilt University Division of Nephrology and Hypertension.

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