Leucine-rich glioma inactivated 3 associates with syntaxin 1
Leucine-rich glioma inactivated 3 associates with syntaxin 1
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DOI：
10.1016/j.neulet.2008.08.044
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发表时间：
2008-10-31
影响因子：
2.5
通讯作者：
Yun, Hye-Young
中科院分区：
文献类型：
--
作者：
Park, Woo-Jae;Lee, Sang Eun;Yun, Hye-Young
富含亮氨酸的胶质瘤失活蛋白3（Leucine-rich glioma inactivated 3，LGI 3）是LGI/epitempin（EPTP）家族成员。LGI 3的生物学功能及其与疾病的关系尚不清楚。我们先前报道了小鼠LGI 3在脑中以发育和转录调节的方式高度表达。在这项研究中，我们确定syntaxin 1，一个SNARE的组成部分，在胞吐，作为一个候选的功能目标LGI 3。用LGI 3抗体对小鼠脑提取物进行的Western印迹分析检测到多种蛋白质形式（75-、60-、35和25-kDa）。蛋白质组学分析，下拉和免疫共沉淀实验确定syntaxin I作为LGI 3相关蛋白。LGI 3与syntaxin I共定位于点状突触模式的皮层神经元的突起中，并在突触体组分中富集。免疫共沉淀显示LGI 3-syntaxin 1复合物不含其他SNARE成分SNAP 25和VAMP 2。重组LGI 3衰减Ca 2 +-诱发的谷氨酸释放从毛地黄皂苷通透的突触体和PC 12细胞转染LGI 3减少K+-诱导的人生长激素的分泌。因此，LGI 3可能通过与突触融合蛋白1的相互作用在神经元胞吐中发挥调节作用。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Leucine-rich glioma inactivated 3 (LGI3) is a member of LGI/epitempin (EPTP) family. The biological function of LGI3 and its association with disease are not known. We previously reported that mouse LGI3 was highly expressed in brain in a developmentally and transcriptionally regulated manner. In this study, we identified syntaxin 1, a SNARE component in exocytosis, as a candidate functional target ofLGI3. Western blot analysis of mouse brain extract with LGI3 antibodies detected multiple protein forms (75-, 60-, 35 and 25-kDa). Proteomic analysis, pull-down and coimmunoprecipitation experiments identified syntaxin I as an LGI3-associated protein. LGI3 colocalized with syntaxin I in processes of cortical neurons with punctate synaptic pattern and was enriched in synaptosomal fraction. Coimmunoprecipitation showed that LGI3-syntaxin 1 complex did not contain other SNARE components, SNAP25 and VAMP2. Recombinant LGI3 attenuated Ca2+-evoked glutamate release from digitonin-permeabilized synaptosomes and transfection of PC12 cells with LGI3 decreased K+-induced secretion of human growth hormone. Thus, LGI3 may play a regulatory role in neuronal exocytosis via its interaction with syntaxin 1. (C) 2008 Elsevier Ireland Ltd. All rights reserved.