Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Engineering Laboratory of Peptides of Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
FASEB J. 2022 Oct;36(10):e22533. doi: 10.1096/fj.202200528R.
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.
在动物禁食期间，营养供应和代谢从碳水化合物转变为新的依赖于能量密集的脂库的分解代谢。βγ-CAT（非晶状体βγ-晶体蛋白和三叶因子的复合物）是在蟾蜍 Bombina maxima 中鉴定出的一种形成孔的蛋白和三叶因子复合物，在严格的调控下组装。在这里，我们确定该蛋白复合物是蟾蜍血液中的固有成分，并且对动物禁食有积极的反应。该蛋白复合物能够促进各种上皮细胞和内皮细胞中的细胞白蛋白和白蛋白结合的脂肪酸（FA）摄取，并且该作用被巨胞饮抑制剂减弱。含有大量富含白蛋白和 FA 的内皮细胞衍生的外泌体，称为营养体，在存在βγ-CAT 的情况下被释放。这些特定的营养体囊泡容易被饥饿的成肌细胞摄取，以支持其存活。结果揭示了形成孔的蛋白βγ-CAT 是一种能够驱动细胞大分子营养物的囊泡内输入和输出的禁食反应元件。
