The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments.
The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments.
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PC6B 胞质结构域包含两个酸性簇，可直接分选至不同的跨高尔基体网络/内体区室。
DOI：
10.1091/mbc.11.4.1257
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发表时间：
2000
影响因子：
3.3
通讯作者：
Thomas,G
中科院分区：
文献类型：
--
作者：
Xiang,Y;Molloy,SS;Thomas,L;Thomas,G
哺乳动物前蛋白转化酶（proprotein convertases，PC）是一类分泌途径的酶，催化肽类激素和许多生物活性蛋白的内水解成熟。两个PC，弗林蛋白酶和PC6 B，广泛表达和共享非常相似的切割位点特异性，这表明它们可能是功能冗余的。然而，生殖细胞基因敲除研究表明，它们不是。在这里，我们报告了不同的亚细胞定位的PC6 B，并确定其胞质结构域（CD）内的分选信息。我们发现，在神经内分泌细胞中，PC6 B定位于一个旁核，布雷菲德菌素A-分散，氯化钡响应后高尔基体网络（TGN）隔室不同弗林蛋白酶和TGN 38。88个氨基酸的PC6 B-cd包含足以将报告蛋白导向与全长PC6 B相同的隔室的分选信息。突变分析表明，胞吞作用主要是由一个典型的酪氨酸基序（Tyr 1802 GluLysLeu）。截断和充分性研究表明，两个集群的酸性氨基酸（AC）内的PC6 B-CD包含差异分选信息。近膜AC（AC 1）指导TGN定位并与TGN分选蛋白PACS-1相互作用。膜远端AC（AC 2）促进全长PC6 B-cd的定位特征。我们的研究结果表明，AC基序可以靶向不同的TGN/内体室的蛋白质，并表明AC介导的PC6 B和弗林蛋白酶的本地化有助于他们在体内的独特作用。
The mammalian proprotein convertases (PCs) are a family of secretory pathway enzymes that catalyze the endoproteolytic maturation of peptide hormones and many bioactive proteins. Two PCs, furin and PC6B, are broadly expressed and share very similar cleavage site specificities, suggesting that they may be functionally redundant. However, germline knockout studies show that they are not. Here we report the distinct subcellular localization of PC6B and identify the sorting information within its cytoplasmic domain (cd). We show that in neuroendocrine cells, PC6B is localized to a paranuclear, brefeldin A–dispersible, BaCl2-responsive post-Golgi network (TGN) compartment distinct from furin and TGN38. The 88-amino acid PC6B-cd contains sorting information sufficient to direct reporter proteins to the same compartment as full-length PC6B. Mutational analysis indicates that endocytosis is predominantly directed by a canonical tyrosine-based motif (Tyr1802GluLysLeu). Truncation and sufficiency studies reveal that two clusters of acidic amino acids (ACs) within the PC6B-cd contain differential sorting information. The membrane-proximal AC (AC1) directs TGN localization and interacts with the TGN sorting protein PACS-1. The membrane-distal AC (AC2) promotes a localization characteristic of the full-length PC6B-cd. Our results demonstrate that AC motifs can target proteins to distinct TGN/endosomal compartments and indicate that the AC-mediated localization of PC6B and furin contribute to their distinct roles in vivo.
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神经内分泌细胞中整合膜肽基甘氨酸α-酰胺化单加氧酶的定位。
影响因子：
4
作者：
Milgram,SL;Kho,ST;Martin,GV;Mains,RE;Eipper,BA
通讯作者：
Eipper,BA
影响因子：
11.4
作者：
MOLLOY, SS;THOMAS, L;THOMAS, G
通讯作者：
THOMAS, G
影响因子：
3.9
作者：
SEIDAH, N;CHRETIEN, M;DAY, R
通讯作者：
DAY, R
弗林蛋白酶定位于跨高尔基体网络并从细胞表面回收涉及细胞质域内的 Ser 和 Tyr 残基 (*)
DOI：
10.1074/jbc.270.47.28397
发表时间：
1995
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Senye Takahashi;T. Nakagawa;T. Banno;Tsuyoshi Watanabe;K. Murakami;K. Nakayama
通讯作者：
K. Nakayama
影响因子：
19
作者：
Molloy, SS;Anderson, ED;Thomas, G
通讯作者：
Thomas, G