Short Elements with Charged Amino Acids Form Clusters to Sort Protachykinin into Large Dense-Core Vesicles
文献类型:期刊论文
作者 | Ma, GQ; Wang, B; Wang, HB; Wang, Q; Bao, L |
刊名 | TRAFFIC
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出版日期 | 2008 |
卷号 | 9期号:12页码:2165-2179 |
关键词 | aggregative signal CGRP large dense-core vesicle protachykinin regulated secretory pathway sorting mechanism |
通讯作者 | Bao, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,baolan@sibs.ac.cn |
英文摘要 | The sorting of neuropeptide tachykinins into large dense-core vesicles (LDCVs) is a key step in their regulated secretion from neurons. However, the sorting mechanism for protachykinin has not yet to be clearly resolved. In this study, we report that the clustered short elements with charged amino acids regulate the efficiency of protachykinin sorting into LDCVs. A truncation experiment showed that the propeptide and the mature peptide-containing sequence of protachykinin were sorted into LDCVs. These two regions exhibit a polarized distribution of charged amino acids. The LDCV localization of the propeptide was gradually decreased with an increasing number of neutral amino acids. Furthermore, the short element with four to five amino acids containing two charged residues was found to be a basic unit for LDCV sorting that enables regulated secretion. In the native propeptide sequence, these charged short elements were clustered to enhance the intermolecular aggregation by electrostatic interaction and produce a gradual and additive effect on LDCV sorting. The optimal conditions for intermolecular aggregation of protachykinin were at millimolar Ca(2+) concentrations and pH 5.5-6.0. These results demonstrate that the charged short elements are clustered such that they serve as aggregative signals and regulate the efficiency of protachykinin sorting into LDCVs. These findings reveal a novel mechanism for the sorting of neuropeptides into a regulated secretory pathway. |
学科主题 | Cell Biology |
类目[WOS] | Cell Biology |
关键词[WOS] | REGULATED SECRETORY PATHWAY ; DISULFIDE-BONDED LOOP ; HYDROPHOBIC-HYDROPHILIC BALANCE ; PH-DEPENDENT AGGREGATION ; GRANULE CONTENT PROTEINS ; DELTA-OPIOID RECEPTORS ; GENE-RELATED PEPTIDE ; TRANS-GOLGI NETWORK ; CARBOXYPEPTIDASE-E ; CHROMOGRANIN-A |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000261086000014 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/1462] ![]() |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Ma, GQ,Wang, B,Wang, HB,et al. Short Elements with Charged Amino Acids Form Clusters to Sort Protachykinin into Large Dense-Core Vesicles[J]. TRAFFIC,2008,9(12):2165-2179. |
APA | Ma, GQ,Wang, B,Wang, HB,Wang, Q,&Bao, L.(2008).Short Elements with Charged Amino Acids Form Clusters to Sort Protachykinin into Large Dense-Core Vesicles.TRAFFIC,9(12),2165-2179. |
MLA | Ma, GQ,et al."Short Elements with Charged Amino Acids Form Clusters to Sort Protachykinin into Large Dense-Core Vesicles".TRAFFIC 9.12(2008):2165-2179. |
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