Amphibian pore-forming protein βγ-CAT drives extracellular nutrient scavenging under cell nutrient deficiency
Ling-Zhen Liu,
Long Liu,
Zhi-Hong Shi,
Xian-Ling Bian,
Zi-Ru Si,
Qi-Quan Wang,
Yang Xiang,
Yun Zhang
Affiliations
Ling-Zhen Liu
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Engineering Laboratory of Peptides of the Chinese Academy of Sciences, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China
Long Liu
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Engineering Laboratory of Peptides of the Chinese Academy of Sciences, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Human Aging Research Institute (HARI) and School of Life Sciences, Nanchang University, Nanchang, Jiangxi 330031, China
Zhi-Hong Shi
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Engineering Laboratory of Peptides of the Chinese Academy of Sciences, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China
Xian-Ling Bian
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Engineering Laboratory of Peptides of the Chinese Academy of Sciences, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China; School of Life Science, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Zi-Ru Si
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Engineering Laboratory of Peptides of the Chinese Academy of Sciences, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China; School of Life Science, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China
Qi-Quan Wang
Human Aging Research Institute (HARI) and School of Life Sciences, Nanchang University, Nanchang, Jiangxi 330031, China
Yang Xiang
Human Aging Research Institute (HARI) and School of Life Sciences, Nanchang University, Nanchang, Jiangxi 330031, China; Corresponding author
Yun Zhang
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Engineering Laboratory of Peptides of the Chinese Academy of Sciences, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650201, China; Corresponding author
Summary: Nutrient acquisition is essential for animal 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, glutamine, and pyruvate deficiency to scavenge extracellular proteins for their nutrient supply and survival. AMPK signaling positively regulated the expression and secretion of βγ-CAT. The PFP complex selectively bound extracellular proteins and promoted proteins 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 proteins. Liposome assays indicated that high concentration of ATP 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 nutrient deficiency by driving vesicular uptake of extracellular proteins, providing a new paradigm for PFPs in cell nutrient acquisition and metabolic flexibility.
