Sorting and processing of secretory proteins.
Sorting and processing of secretory proteins.
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DOI：
10.1042/bj2990001
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发表时间：
1994-04
期刊：
影响因子：
--
通讯作者：
P. Halban;J. Irminger
中科院分区：
文献类型：
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作者：
P. Halban;J. Irminger
蛋白质代谢途径：概述前导和无前导的分泌蛋白大多数分泌蛋白是作为携带前导肽或信号肽的前体合成的。正是信号肽与核糖体上的同源蛋白复合物（SRP或信号识别颗粒）的相互作用确保了分泌蛋白在RER上合成并移位到该细胞器的内腔中，最典型的是随着翻译的进行[1-5]。信号肽被信号肽酶切割之后迅速发生。在RER中，分泌蛋白将在伴侣蛋白的协助下折叠成它们的三级结构[6-11]。低聚物也发生在该隔室中[8]。对于许多分泌性蛋白质，糖基化起始于粗面内质网内，并进行到高尔基体。虽然糖基化不是分泌蛋白质的必需条件，（非糖基化分泌蛋白质的一个充分研究的例子是胰岛素原），哺乳动物糖基化突变体的研究极大地促进了分泌途径早期步骤的阐明[12]。有一种质量控制程序，可以确保以某种方式受损或不完全折叠，或未能正确寡聚化的蛋白质，没有被运出RER [6，8]。这种改变的蛋白质通常在前高尔基体降解区室中降解[13，14]。在过去的几年里，很明显，在几种甚至所有的细胞类型中都存在分泌蛋白经典途径的替代途径[15-17]。这种新的途径被缺乏常规疏水信号序列的分泌性蛋白质所采用，包括碱性成纤维细胞生长因子和白细胞介素-1。尽管分泌的精确机制仍有待鉴定，但似乎这些蛋白质可以通过以下途径直接从胞质溶胶中分泌：
PROTEIN SECRETORY PATHWAYS: A GENERAL OUTLINE Leader and leaderless secretory proteins Most secretory proteins are synthesized as precursors carrying a leader, or signal, peptide. It is the interaction of the signal peptide with its cognate protein complex (SRP or signal rec-ognition particle) on the ribosome which assures that secretory proteins are synthesized on the RER and translocated into the lumen of this organelle, most typically as translation proceeds [1-5]. The cleavage of the signal peptide by signal peptidase occurs rapidly thereafter. It is in the RER that secretory proteins will become folded into their tertiary structure, assisted by chaperone proteins [6-11]. Oligomerization also occurs in this compartment [8]. For many secretory proteins, glycosylation is initiated within the RER and proceeds up to the trans-Golgi. Although glycosylation is not mandatory for secretory proteins (a well studied example of a non-glycosylated secretory protein being proinsulin), the study ofmammalian glycosylation mutants has greatly facilitated the elucidation of the early steps in the secretory pathway [12].There is a quality control procedure that ensures that proteins which are in some way damaged or incompletely folded, or have failed to oligomerize correctly, are not transported out of the RER [6, 8]. Such altered proteins are typically degraded in the pre-Golgi degradation compartment [13, 14]. Over the past few years, it has become apparent that an alternative to this classicalpathway for secretory proteins exists in several, and perhaps all, cell types [15-17]. This novel pathway is employed by secretory proteins which lack a conventional hydrophobic signal sequence, including basic fibroblast growth factor and interleukin-1. Although the precise mechanism of secretion remains to be characterized, it appears that such proteins may be secreted directly from the cytosol via either