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支架蛋白 SYD-2/Liprin-α 调节线虫运动神经元中致密核心囊泡的流动性和极化分布。

The scaffolding protein SYD-2/Liprin-α regulates the mobility and polarized distribution of dense-core vesicles in C. elegans motor neurons.

机构信息

Department of Molecular Physiology and Pharmacology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA.

出版信息

PLoS One. 2013;8(1):e54763. doi: 10.1371/journal.pone.0054763. Epub 2013 Jan 24.

DOI:10.1371/journal.pone.0054763
PMID:23358451
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3554613/
Abstract

The polarized trafficking of axonal and dendritic components is essential for the development and maintenance of neuronal structure and function. Neuropeptide-containing dense-core (DCVs) vesicles are trafficked in a polarized manner from the cell body to their sites of release; however, the molecules involved in this process are not well defined. Here we show that the scaffolding protein SYD-2/Liprin-α is required for the normal polarized localization of Venus-tagged neuropeptides to axons of cholinergic motor neurons in C. elegans. In syd-2 loss of function mutants, the normal polarized localization of INS-22 neuropeptide-containing DCVs in motor neurons is disrupted, and DCVs accumulate in the cell body and dendrites. Time-lapse microscopy and kymograph analysis of mobile DCVs revealed that syd-2 mutants exhibit decreased numbers of DCVs moving in both anterograde and retrograde directions, and a corresponding increase in stationary DCVs in both axon commissures and dendrites. In addition, DCV run lengths and velocities were decreased in both axon commissures and dendrites of syd-2 mutants. This study shows that SYD-2 promotes bi-directional mobility of DCVs and identifies SYD-2 as a novel regulator of DCV trafficking and polarized distribution.

摘要

轴突和树突成分的极化运输对于神经元结构和功能的发育和维持至关重要。含有神经肽的致密核心 (DCV) 囊泡以极化的方式从细胞体运输到其释放部位；然而，参与这个过程的分子尚未明确。在这里，我们表明支架蛋白 SYD-2/Liprin-α 对于秀丽隐杆线虫中胆碱能运动神经元中 Venus 标记的神经肽向轴突的正常极化定位是必需的。在 syd-2 功能丧失突变体中，运动神经元中 INS-22 神经肽含有 DCV 的正常极化定位被破坏，DCV 在细胞体和树突中积累。对可移动 DCV 的延时显微镜和 kymograph 分析表明，syd-2 突变体中向前和向后移动的 DCV 数量减少，并且在轴突交叉处和树突中的静止 DCV 相应增加。此外，syd-2 突变体的轴突交叉处和树突中的 DCV 运行长度和速度均降低。这项研究表明，SYD-2 促进 DCV 的双向迁移，并将 SYD-2 鉴定为 DCV 运输和极化分布的新型调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f5c/3554613/57effdade311/pone.0054763.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f5c/3554613/57effdade311/pone.0054763.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f5c/3554613/57effdade311/pone.0054763.g008.jpg

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