Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform
Definition of Munc13-homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform
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DOI：
10.1042/0264-6021:3490247
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发表时间：
2000-07-01
影响因子：
4.1
通讯作者：
Brose, N
中科院分区：
文献类型：
--
作者：
Koch, H;Hofmann, K;Brose, N
Munc13 蛋白构成了三个高度同源分子（Munc13-1、Munc13-2 和 Munc13-3）的家族。除了普遍表达的 Munc13-2 剪接变体之外，Munc13 蛋白具有脑特异性。 Munc13-1 在谷氨酸能突触的突触小泡胞吐作用中具有中枢启动功能。为了鉴定可调节非谷氨酸能神经元或非神经元细胞中的分泌过程的 Munc13 样蛋白，我们开发了两个 Munc13 同源域 (MHD) 的蛋白质谱。 MHD 存在于多种蛋白质中，其中一些蛋白质先前已与膜运输反应有关。利用人类表达序列标签（EST）数据库中的部分序列，我们表征了一种新型的、普遍表达的大鼠蛋白（Munc13-4），该蛋白属于Munc13样分子的亚家族，其中典型的Munc13样结构域结构是保守的。 Munc13-4 主要在肺中表达，定位于支气管上皮的杯状细胞和肺泡 II 型细胞，这两种细胞都是具有分泌功能的细胞类型。在本研究中，我们鉴定了一组新蛋白质，其中一些可能以类似 Munc13 的方式发挥作用来调节膜运输。本研究中描述的 MHD 图谱是鉴定 Munc13 样蛋白的有用工具，否则这些蛋白将无法被检测到。
Munc13 proteins constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3). With the exception of a ubiquitously expressed Munc13-2 splice variant, Munc13 proteins are brain-specific. Munc13-1 has a central priming function in synaptic vesicle exocytosis from glutamatergic synapses. In order to identify Munc13-like proteins that may regulate secretory processes in non-glutamatergic neurons or non-neuronal cells, we developed protein profiles for two Munc13-homology-domains (MHDs). MHDs are present in a wide variety of proteins, some of which have previously been implicated in membrane trafficking reactions. Taking advantage of partial sequences in the human expressed sequence tag (EST) database, we characterized a novel, ubiquitously expressed, rat protein (Munc13-4) that belongs to a subfamily of Munc13-like molecules, in which the typical Munc13-like domain structure is conserved. Munc13-4 is predominantly expressed in lung where it is localized to goblet cells of the bronchial epithelium and to alveolar type II cells, both of which are cell types with secretory function. In the present study we identify a group of novel proteins, some of which may function in a Munc13-like manner to regulate membrane trafficking. The MHD profiles described in the present study are useful tools for the identification of Munc13-like proteins, that would otherwise have remained undetected.