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

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, βγ‐CAT (a complex of non‐lens βγ‐crystallin and trefoil factor) 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 (FA) 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 FAs, called nutrisomes, were released in the presence of βγ‐CAT. These specific nutrient vesicles were readily taken up by starved myoblast cells to support their survival. The results uncovered that pore‐forming protein βγ‐CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.