Novel rabphilin-3-like protein associates with insulin-containing granules in pancreatic beta cells
Novel rabphilin-3-like protein associates with insulin-containing granules in pancreatic beta cells
复制标题
DOI：
10.1074/jbc.274.40.28542
复制
发表时间：
1999-10-01
影响因子：
4.8
通讯作者：
Izumi, T
中科院分区：
文献类型：
--
作者：
Wang, J;Takeuchi, T;Izumi, T
通过比较胰腺α和β细胞系中表达的基因，利用mRNA差异显示技术在胰腺β细胞中发现了一种新的rabphilin-3样基因granuphilin。granuphilin基因蛋白产物的结构域结构与rabphilin-3基因相似，含有氨基末端锌指基序和羧基末端c- 2结构域。有两种亚型：较大的亚型Granuphilin -a具有两个c -2结构域，而较小的亚型Granuphilin -b仅包含第一个c -2结构域。Granuphilin在胰腺β细胞和垂体中特异性表达，但在胰腺α细胞、肾上腺或其他主要器官如大脑中不表达。部分嗜颗粒蛋白与含胰岛素的致密核颗粒相关，但与β细胞中的突触样微泡无关，因此，其分布模式与rabphilin-3的分布模式形成鲜明对比，rabphilin-3与神经元中的小突触小泡相关。嗜颗粒蛋白的第一个c -2结构域以不依赖于Ca2+的方式结合磷脂，而第二个结构域则不是。嗜颗粒蛋白的这些特征表明，它不是内分泌细胞中rabphilin-3的简单对应物，它在内分泌组织中致密核颗粒的胞外分泌调节中具有独特的作用。
A novel rabphilin-3-like gene, granuphilin, has been identified in pancreatic beta cells by comparing genes expressed in pancreatic alpha and beta cell lines using mRNA differential display. The domain structure of the protein products of the granuphilin gene contains an amino-terminal zinc-finger motif and carboxyl-terminal C-2-domains, similar to that of the rabphilin-3 gene. There are two isoforms: the larger isoform, granuphilin-a, has two C-2-domains, whereas the smaller one, granuphilin-b, contains only the first C-2-domain, Granuphilin is specifically expressed in pancreatic beta cells and the pituitary gland, but not in pancreatic alpha cells, the adrenal gland, or other major organs such as the brain. A portion of granuphilin associates with insulin-containing dense-core granules, but not with synaptic-like microvesicles in beta cells, Thus, its distribution pattern presents a striking contrast with that of rabphilin-3, which associates with small synaptic vesicles in neurons. The first C-2-domain of granuphilin binds phospholipids in a Ca2+-independent manner, whereas the second one does not. These distinctive characteristics of granuphilin suggest that it is not a simple counterpart of rabphilin-3 in endocrine cells and that it has a unique role in the regulated exocytosis of dense-core granules in endocrine tissues.