The Role of BiP Retrieval by the KDEL Receptor in the Early Secretory Pathway and its Effect on Protein Quality Control and Neurodegeneration.
The Role of BiP Retrieval by the KDEL Receptor in the Early Secretory Pathway and its Effect on Protein Quality Control and Neurodegeneration.
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DOI：
10.3389/fnmol.2017.00222
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发表时间：
2017
影响因子：
4.8
通讯作者：
Aoe T
中科院分区：
文献类型：
--
作者：
Jin H;Komita M;Aoe T
早期分泌途径中的蛋白质质量控制是真核生物适应内质网（ER）应激的普遍机制。免疫球蛋白重链结合蛋白（BiP）是这一过程中的重要组成部分之一。BiP与新生蛋白质相互作用以促进其折叠。BiP还在防止错误折叠蛋白聚集和调节细胞遭受各种损伤时的ER应激反应中起重要作用。BiP是存在于ER中的分子伴侣的70-kDa热休克蛋白（HSP 70）家族的成员。BiP和未折叠蛋白之间的相互作用由底物结合结构域和ATP酶活性的核苷酸结合结构域介导，导致蛋白质折叠和成熟。BiP在其羧基末端也具有一个修复基序。当BiP从ER分泌时，ER后区室中的Lys-Asp-Glu-Leu（KDEL）受体与BiP的羧基末端KDEL序列结合，并通过外壳蛋白复合物I（COPI）囊泡转运将BiP返回ER。虽然酵母研究表明，通过KDEL受体的BiP检索在单细胞中不是必需的，但它对多细胞生物至关重要，其中一些必需的蛋白质需要检索以促进折叠和成熟。在敲入小鼠表达突变体BiP与检索基序删除的实验揭示了独特的作用，BiP检索KDEL受体在神经元发育和年龄相关的神经退行性变。
Protein quality control in the early secretory pathway is a ubiquitous eukaryotic mechanism for adaptation to endoplasmic reticulum (ER) stress. An ER molecular chaperone, immunoglobulin heavy chain-binding protein (BiP), is one of the essential components in this process. BiP interacts with nascent proteins to facilitate their folding. BiP also plays an important role in preventing aggregation of misfolded proteins and regulating the ER stress response when cells suffer various injuries. BiP is a member of the 70-kDa heat shock protein (HSP70) family of molecular chaperones that resides in the ER. Interaction between BiP and unfolded proteins is mediated by a substrate-binding domain and a nucleotide-binding domain for ATPase activity, leading to protein folding and maturation. BiP also possesses a retrieval motif in its carboxyl terminal. When BiP is secreted from the ER, the Lys-Asp-Glu-Leu (KDEL) receptor in the post-ER compartments binds with the carboxyl terminal KDEL sequence of BiP and returns BiP to the ER via coat protein complex I (COPI) vesicular transport. Although yeast studies showed that BiP retrieval by the KDEL receptor is not essential in single cells, it is crucial for multicellular organisms, where some essential proteins require retrieval to facilitate folding and maturation. Experiments in knock-in mice expressing mutant BiP with the retrieval motif deleted revealed a unique role of BiP retrieval by the KDEL receptor in neuronal development and age-related neurodegeneration.
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BIP介导的分子机制的内质网的Sec61易位门控。
DOI：
10.1083/jcb.200409174
发表时间：
2005-01-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
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Johnson AE
DOI：
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发表时间：
2009-09-15
影响因子：
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作者：
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影响因子：
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作者：
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作者：
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作者：
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