id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-102178-ju826pao	Carey, Clayton M.	Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis	2020-03-30		.txt	text/plain	5255	240	46	Under normal conditions, GC-C interacts with endogenous guanylin peptides to promote water secretion in the intestine, but signaling can be hijacked by bacterially-encoded heat-stable enterotoxins (STa) during infection, which leads to overstimulation of GC-C and diarrhea. Phylogenetic analysis in mammals revealed evidence of recurrent positive selection in the GC-C ligand-binding domain in primates and bats, consistent with selective pressures to evade interactions with STa. Using in vitro assays and transgenic intestinal organoids to model STa-mediated diarrhea, we show that GC-C diversification in these lineages results in substantial variation in toxin susceptibility. Under normal conditions, GC-C activity is stimulated by interactions with the endogenous peptides guanylin and uroguanylin, leading to an increase in intracellular cGMP levels in enterocytes lining the small intestine and colon 3 ( Figure 1A ). To test if rapid evolution of GC-C ligand-binding domains result in functional differences in STa susceptibility, we generated cell lines stably expressing GC-C from seven primate and five bat species.	./cache/cord-102178-ju826pao.txt	./txt/cord-102178-ju826pao.txt