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

doi:10.1016/j.isci.2023.106598

Amphibian pore-forming protein βγ-CAT drives extracellular nutrient scavenging under cell nutrient deficiency

iScience. 2023 Apr 7;26(5):106598. doi: 10.1016/j.isci.2023.106598. eCollection 2023 May 19.

Authors

Ling-Zhen Liu^{1

2}, Long Liu^{1

3}, Zhi-Hong Shi^{1

2}, Xian-Ling Bian^{1

4}, Zi-Ru Si^{1

4}, Qi-Quan Wang³, Yang Xiang³, Yun Zhang^{1

2

5}

Affiliations

¹ 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.
² Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
³ Human Aging Research Institute (HARI) and School of Life Sciences, Nanchang University, Nanchang, Jiangxi 330031, China.
⁴ School of Life Science, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230026, China.
⁵ Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.

Abstract

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.

Keywords: Cell biology.