Protein quality control mechanisms and protein storage in the endoplasmic reticulum. A conflict of interests?
Protein quality control mechanisms and protein storage in the endoplasmic reticulum. A conflict of interests?
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DOI：
10.1104/pp.104.050351
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发表时间：
2004-11-01
期刊：
影响因子：
7.4
通讯作者：
Ceriotti, A
中科院分区：
文献类型：
--
作者：
Vitale, A;Ceriotti, A
30多年前，人们观察到玉米（Zea mays）种子的储存蛋白以发育中的胚乳细胞的“沿着内质网池的凸起或局部扩张”的形式积累（Khoo和Wolf，1970）。后来发现，广泛存在的 7S 和 11S 类种子储存蛋白从内质网 (ER) 到达高尔基复合体，然后沉积在液泡中，而许多谷物储存蛋白却在内质网腔内形成电子密集的圆形结构，直径为 0.5 至 2.0 毫米，称为蛋白体（Herman 和 Lakins，1999）。然后，这些大的聚集体要么永久储存在内质网中，要么通过非常规的蛋白质运输途径输送到储存液泡。如今，一些对人类营养最重要的蛋白质在内质网内形成蛋白体的机制仍然是细胞生物学中一个令人着迷但仍然令人困惑的问题。这种利用内质网以高度浓缩的形式储存大量特定蛋白质的发育程序仅在植物中发现。另一方面，由于应激或遗传缺陷，内质网中新合成的蛋白质聚集通常被细胞视为一种病理，必须通过处理错误折叠的蛋白质来避免这种病理（Sitia 和 Braakman，2003）。许多内质网驻留蛋白确实具有防止蛋白质聚集的作用，将新生和新合成的多肽维持在与进一步结构成熟相容的状态，或者对于有缺陷的蛋白质来说，与降解相容。因此，用于储存在内质网中的蛋白质必须进化为以受控方式凝结，从而避免从内质网输出和降解。如何实现这一目标是本次更新的主题。内质网是内膜系统的一部分，内膜系统还包括高尔基复合体、液泡和质膜作为主要组成部分。该系统拥有分泌途径，该途径合成上述区室和细胞壁的大部分蛋白质并将其输送到正确的位置。这些蛋白质统称为分泌蛋白。内质网起着蛋白质苗圃的作用，在新合成的分泌蛋白运输到高尔基复合体，然后运输到液泡或细胞表面之前协助折叠和组装（Vitale 和 Denecke，1999）。 ER 中的许多居民都有促进其在该区室中定位的信号（Vitale 和 Denecke，1999），但 ER 内积累的储存蛋白不携带任何这些已知信号。它们如何在 ER 中形成稳定的结构？为了尝试回答这个问题，我们需要考虑内质网功能及其调节的许多方面。
More than 30 years ago it was observed that the storage proteins of maize (Zea mays) seeds accumulate as ‘‘bulges or localized dilatations along the endoplasmic reticulum cisternae’’of developing endosperm cells (Khoo and Wolf, 1970). It later became evident that, whereas the widespread seed storage proteins of the 7S and 11S classes travel from the endoplasmic reticulum (ER) to the Golgi complex and are then deposited in vacuoles, a number of cereal storage proteins instead form electron-dense, round-shaped structures with diameters of 0.5 to 2.0 mm, termed protein bodies, within the ER lumen (Herman and Larkins, 1999). These large aggregates are then either permanently stored in the ER or delivered to storage vacuoles by unconventional protein traffic pathways. Today, the mechanisms by which some of the most important proteins for human nutrition form protein bodies within the ER remain a fascinating but still puzzling issue in cell biology. This developmentally programmed use of the ER to store vast amounts of specific proteins in highly condensed forms has been found only in plants. On the other hand, aggregation of newly synthesized proteins in the ER, due to stress or genetic defects, is usually treated by the cell as a pathology that must be avoided by disposing of the misfolded proteins (Sitia and Braakman, 2003). Many ER resident proteins indeed have the role of preventing protein aggregation, maintaining nascent and newly synthesized polypeptides in a state that is compatible with further structural maturation or, for defective proteins, with degradation. Thus, proteins destined for storage in the ER must have evolved to condense in a controlled fashion and thus to avoid both export from the ER and degradation. How this might be achieved is the topic of this update. The ER is part of the endomembrane system, which also includes the Golgi complex, vacuoles, and the plasma membrane as major components. The system hosts the secretory pathway, which synthesizes and delivers to the correct location most of the proteins of the above-mentioned compartments and of the cell wall. These proteins are collectively termed secretory proteins. The ER plays the role of a protein nursery, assisting in the folding and assembly of newly synthesized secretory proteins before they traffic to the Golgi complex and then the vacuoles or the cell surface (Vitale and Denecke, 1999). Many residents of the ER have signals that promote their localization in this compartment (Vitale and Denecke, 1999), but storage proteins that accumulate within the ER do not carry any of these known signals. How do they form stable structures in the ER? To try answering, we need to take into consideration many aspects of ER functions and their regulation.