Pore-forming protein βγ-CAT drives extracellular nutrient scavenging under cell starvation

Abstract

AbstractNutrient acquisition is essential for cells. βγ-CAT is a pore-forming protein (PFP) and trefoil factor complex assembled under tight regulation identified in toad Bombina maxima. Here, we reported that B. maxima cells secreted βγ-CAT under glucose and glutamine deficiency to scavenge extracellular proteins for their nutrient supply and survival. AMP-activated kinase signaling positively regulated the expression and secretion of βγ-CAT. The PFP complex promoted albumin and ovalbumin uptake through endolysosomal pathways. Elevated intracellular amino acids, enhanced ATP production, and eventually prolonged cell survival were observed in the presence of βγ-CAT and extracellular albumin or ovalbumin. Liposome assays indicated that high concentration of ATP (around 1–5 mM) negatively regulated the opening of βγ-CAT channels. Collectively, these results uncovered that βγ-CAT is an essential element in cell nutrient scavenging under cell starvation by driving vesicular uptake of extracellular proteins, providing a new paradigm for PFPs in cell nutrient acquisition and metabolic flexibility.