Pore-forming protein βγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients

Abstract

During animal fasting, the nutrient supply and metabolism switch from carbohydrates to a new reliance on the catabolism of energy-dense lipid stores. Assembled under tight regulation, {beta}{gamma}-CAT is a pore-forming protein and trefoil factor complex identified in toad Bombina maxima. Here, we determined that this protein complex is a constitutive component in toad blood, that actively responds to the animal fasting. The protein complex was able to promote cellular albumin and albumin-bound fatty acid uptake in a variety of epithelial and endothelial cells, and the effects were attenuated by a macropinocytosis inhibitor. Endothelial cell-derived exosomes containing largely enriched albumin and fatty acids, called nutrisomes, were released in the presence of {beta}{gamma}-CAT. These specific nutrient vesicles were readily taken by starved muscle cells to support their survival. The results uncovered that pore-forming protein {beta}{gamma}-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.