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bioRxiv · 10.1101/2022.07.20.500773

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

Liu, L.-Z.·Liu, L.·Shi, Z.-H.·Bian, X.-L.·Wang, Q.-Q.·Xiang, Y.·Zhang, Y.
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Abstract

Nutrient acquisition is essential for cells. {beta}{gamma}-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 {beta}{gamma}-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 {beta}{gamma}-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 {beta}{gamma}-CAT and extracellular albumin or ovalbumin. Liposome assays indicated that high concentration of ATP (around 1-5 mM) negatively regulated the opening of {beta}{gamma}-CAT channels. Collectively, these results uncovered that {beta}{gamma}-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.

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Liu, L.-Z., Liu, L., Shi, Z.-H., Bian, X.-L., Wang, Q.-Q., Xiang, Y., Zhang, Y.. 2022-07-21. Pore-forming protein βγ-CAT drives extracellular nutrient scavenging under cell starvation. https://doi.org/10.1101/2022.07.20.500773

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