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A cell-specific transgenic approach in Xenopus reveals the importance of a functional p24 system for a secretory cell

机译:非洲爪蟾的细胞特异性转基因方法揭示了分泌性细胞功能性p24系统的重要性

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The p24alpha, -beta, -gamma, and -delta proteins are major multimeric constituents of cycling endoplasmic reticulum-Golgi transport vesicles and are thought to be involved in protein transport through the early secretory pathway. In this study, we targeted transgene overexpression of p24delta(2) specifically to the Xenopus intermediate pituitary melanotrope cell that is involved in background adaptation of the animal and produces high levels of its major secretory cargo proopiomelanocortin (POMC). The transgene product effectively displaced the endogenous p24 proteins, resulting in a melanotrope cell p24 system that consisted predominantly of the transgene p24delta(2) protein. Despite the severely distorted p24 machinery, the subcellular structures as well as the level of POMC synthesis were normal in these cells. However, the number and pigment content of skin melanophores were reduced, impairing the ability of the transgenic animal to fully adapt to a black background. This physiological effect was likely caused by the affected profile of POMC-derived peptides observed in the transgenic melanotrope cells. Together, our results suggest that in the early secretory pathway an intact p24 system is essential for efficient secretory cargo transport or for supplying cargo carriers with the correct protein machinery to allow proper secretory protein processing. [References: 53]
机译:p24alpha,-beta,-gamma和-delta蛋白是循环内质网-高尔基体运输小泡的主要多聚体成分,被认为与蛋白质通过早期分泌途径的运输有关。在这项研究中,我们针对p24delta(2)的转基因过度表达专门针对非洲爪蟾中间垂体黑素体细胞,该细胞参与动物的背景适应,并产生高水平的主要分泌性货物原黑素皮质激素(POMC)。转基因产物有效地取代了内源性p24蛋白,形成了一个由黑色素细胞构成的p24系统,该系统主要由转基因p24delta(2)蛋白组成。尽管p24机制严重变形,但这些细胞中的亚细胞结构以及POMC合成水平还是正常的。然而,皮肤黑素细胞的数目和色素含量减少,损害了转基因动物完全适应黑色背景的能力。这种生理效应很可能是由于在转基因黑素体细胞中观察到的POMC衍生肽的受影响所致。总之,我们的结果表明,在早期分泌途径中,完整的p24系统对于有效的分泌性货物运输或为载货船提供正确的蛋白质机制以允许适当的分泌性蛋白质加工至关重要。 [参考:53]

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