Spending your days examining mouse diarrhea is not most people's idea of a worthwhile endeavor; but, at least for Toivola et al. (page 911), the activity has proven highly productive. By doing so, they have uncovered a possible protein sorting function for intestinal keratin 8 (K8), the major keratin of the digestive system.
Keratin knockouts are more famous for leaky skin than soft stools. But removal of these intermediate filament proteins has myriad effects, and loose stools is one consequence of removing K8. The team exploited this phenotype to investigate the cellular mechanisms associated with intestinal keratin function. Through a series of electrophysiological, immunofluorescence, and biochemical studies, they concluded that a lack of keratin filaments in the colon leads to defects in electrogenic transport—such as chloride secretion instead of absorption and altered anion exchanger expression—due to protein mistargeting. This is followed by hyperproliferation and inflammation of the colonic epithelium.
Given that transporter redistribution occurred long before inflammation and hyperproliferation, the group proposes that transporter defects give rise to changes in pH leading to hyperproliferation. It remains to be determined whether K8 possesses a similar targeting function in other tissues such as the liver and pancreas, or whether its function depends on the epithelial tissue involved. ▪