Decreased basal mucus secretion by Slp2-a-deficient gastric surface mucous cells
Decreased basal mucus secretion by Slp2-a-deficient gastric surface mucous cells
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DOI：
10.1111/j.1365-2443.2006.00964.x
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发表时间：
2006-06-01
期刊：
影响因子：
2.1
通讯作者：
Fukuda, Mitsunori
中科院分区：
文献类型：
--
作者：
Saegusa, Chika;Tanaka, Toru;Fukuda, Mitsunori
突触结合蛋白样蛋白（Synaptotagmin-like protein，Slp）2-a是Rab 27 A/B的一种效应蛋白，参与细胞内膜转运。然而，Slp 2-a蛋白的精确组织分布及其功能在很大程度上仍然未知。在本研究中，我们使用特异性抗Slp 2-a抗体来研究Slp 2-a在小鼠中的组织分布，并且发现Slp 2-a在小鼠胃中最丰富地表达。免疫共沉淀实验表明Slp 2-a与Rab 27 A/B在体内相互作用。我们还发现Slp 2-a和Rab 27 A/B主要定位于胃表面粘液细胞的顶端区域，在那里粘液颗粒积聚。通过同源重组产生的Slp 2-a突变小鼠的分析显示粘液颗粒的数量减少，与胃表面粘液细胞中的顶端质膜对接的颗粒的缺乏，以及Slp 2-a缺陷型胃原代细胞的粘液分泌减少。基于这些结果，我们提出Slp 2-a是小鼠胃表面粘液细胞中粘蛋白分泌机制的一部分。
Synaptotagmin-like protein (Slp) 2-a is a putative Rab27A/B-effector protein and is implicated in intracellular membrane transport. However, the precise tissue distribution of Slp2-a protein and its functions remain largely unknown. In this study we used a specific anti-Slp2-a antibody to investigate the tissue distribution of Slp2-a in mice and found that Slp2-a is most abundantly expressed in mouse stomach. Co-immunoprecipitation experiments indicated that Slp2-a interacts with Rab27A/B in vivo. We also discovered that Slp2-a and Rab27A/B are predominantly localized at the apical region of gastric-surface mucous cells, where mucus granules are accumulated. Analysis of Slp2-a mutant mice generated by homologous recombination showed a reduced number of mucus granules, a deficiency of granule docking with the apical plasma membrane in the gastric-surface mucous cells and reduction of mucus secretion by Slp2-a-deficient gastric primary cells. Based on these results, we propose that Slp2-a is part of the mucin secretory machinery in surface mucous cells of mouse stomach.