Pore-forming protein βγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients
Pore-forming protein βγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients
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成孔蛋白 βγ-CAT 对禁食迅速做出反应，具有提供大分子营养物质的能力
DOI：
10.1096/fj.202200528r
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发表时间：
2022-10-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Shi, Zhi-Hong;Zhao, Zhong;Zhang, Yun
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脂质储存的分解代谢。β - γ - cat（非晶态β - γ -晶体蛋白和三叶因子的复合体）是在蟾蜍bomina maxima中发现的一种成孔蛋白和三叶因子复合体，在严格的调控下组装。在这里，我们确定这种蛋白质复合物是蟾蜍血液中的组成成分，对动物禁食有积极反应。该蛋白复合物能够促进多种上皮细胞和内皮细胞对细胞白蛋白和白蛋白结合脂肪酸（FA）的摄取，而这种作用被巨噬细胞增多症抑制剂减弱。内皮细胞来源的外泌体含有大量富集的白蛋白和FAs，称为营养体，在β - γ - cat存在下被释放。这些特定的营养囊泡很容易被饥饿的成肌细胞吸收，以支持它们的生存。结果发现，成孔蛋白β - γ - cat是一种快速响应元件，能够驱动细胞囊泡输入和输出大分子营养物质。
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, beta gamma-CAT (a complex of non-lens beta gamma-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 beta gamma-CAT. These specific nutrient vesicles were readily taken up by starved myoblast cells to support their survival. The results uncovered that pore-forming protein beta gamma-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.