
胰岛β细胞表达生成的PICK1和胰岛素颗粒合并在一起
胰岛素是调节血糖的主要激素,胰岛素分泌不足会造成糖尿病。胰岛素的前体是胰岛素原,通过内质网和高尔基体的加工,zui终被包裹形成胰岛素颗粒。胰岛素颗粒是一种致密的核心囊泡。但是胰岛素颗粒的生物合成和成熟的分子机制依然不是很清楚。
在该研究中,研究人员发现了两个包浆蛋白PICK1 和 ICA69,它们被认为参与调节胰岛素颗粒的生物合成和成熟加工。PICK1和ICA69都有一个香蕉形的BAR结构域,这个结构域可以弯曲脂质膜,促进致密核心囊泡的成熟加工。
研究表明,如果缺少了PICK1 和 ICA69两者中的任何一种,胰岛素颗粒就不能顺利的形成,这样导致的结果就是,胰岛素原不能转变成成熟的胰岛素。缺乏PICK1 或者 ICA69基因的小鼠,它们的血糖会升高,这在糖尿病患者中也是一个很显著的特点。所以,结合以往的研究表明,PICK1对于颗粒的形成非常重要,同时PICK1 和 ICA69在调节致密核心囊泡的生物合成和成熟中发挥着非常重要的作用。
PICK1 and ICA69 Control Insulin Granule Trafficking and Their Deficiencies Lead to Impaired Glucose Tolerance
Mian Cao equal contributor, Zhuo Mao equal contributor, Chuen Kam, Nan Xiao, Xiaoxing Cao, Chong Shen, Kenneth K. Y. Cheng, Aimin Xu, Kwong-Man Lee, Liwen Jiang,Jun Xia
Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A