Polypyrimidine tract-binding protein promotes insulin secretory granule biogenesis
Polypyrimidine tract-binding protein promotes insulin secretory granule biogenesis
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DOI：
10.1038/ncb1099
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发表时间：
2004-03-01
影响因子：
21.3
通讯作者：
Solimena, M
中科院分区：
文献类型：
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作者：
Knoch, KP;Bergert, H;Solimena, M
胰腺β细胞将胰岛素储存在分泌颗粒中，在葡萄糖刺激时分泌颗粒进行胞吐。持续的刺激会耗尽β细胞的颗粒池，必须迅速恢复。然而，促进快速颗粒生物合成的因素是未知的。在这里，我们表明，β细胞刺激诱导核质易位的多嘧啶道结合蛋白（PTB）。活化的胞质PTB结合并稳定分泌颗粒蛋白质编码mRNA，从而增加其翻译，而通过RNA干扰（RNAi）敲低PTB表达导致分泌颗粒的耗尽。这些发现可能为理解和治疗糖尿病提供见解，其中胰岛素分泌通常受损。
Pancreatic beta-cells store insulin in secretory granules that undergo exocytosis upon glucose stimulation. Sustained stimulation depletes beta-cells of their granule pool, which must be quickly restored. However, the factors promoting rapid granule biogenesis are unknown. Here we show that beta-cell stimulation induces the nucleocytoplasmic translocation of polypyrimidine tract-binding protein (PTB). Activated cytosolic PTB binds and stabilizes mRNAs encoding proteins of secretory granules, thus increasing their translation, whereas knockdown of PTB expression by RNA interference (RNAi) results in the depletion of secretory granules. These findings may provide insight for the understanding and treatment of diabetes, in which insulin secretion is typically impaired.