AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila.
AP-1 and clathrin are essential for secretory granule biogenesis in Drosophila.
复制标题
DOI：
10.1091/mbc.e11-01-0054
复制
发表时间：
2011-06-15
影响因子：
3.3
通讯作者：
Brill JA
中科院分区：
文献类型：
--
作者：
Burgess J;Jauregui M;Tan J;Rollins J;Lallet S;Leventis PA;Boulianne GL;Chang HC;Le Borgne R;Krämer H;Brill JA
在果蝇幼虫唾液腺细胞中形成粘液型分泌颗粒需要笼蛋白和AP-1。Clathrin和AP-1与分泌物共存于跨高尔基体网络(TGN)和未成熟颗粒。此外，TGN需要AP-1才能招募到笼养蛋白。引人注目的是，AP-1或笼状蛋白的缺失严重阻碍了颗粒的生物发生。 调节的激素、消化酶和其他生物活性分子的分泌需要形成分泌颗粒。网状蛋白和网状蛋白适配器蛋白复合体1(AP-1)是外分泌、内分泌和神经内分泌颗粒成熟所必需的。然而，分泌颗粒生物发生的最初步骤只被最少了解。利用果蝇黑腹果蝇强大的遗传学手段，研究了三龄幼虫唾液腺上皮细胞内形成的含有粘蛋白的“胶粒”的生物发生的分子途径。Clathrin和AP-1在跨高尔基体网络(TGN)上共定位，并且需要AP-1才能招募到clathrin。此外，笼状蛋白和AP-1与分泌物共存于TGN和未成熟颗粒上。最后，网状蛋白或AP-1的缺失会导致分泌颗粒形成的严重障碍。这些发现确立了AP-1和笼蛋白依赖的运输在含有粘蛋白的分泌颗粒的生物发生中的新作用。
Clathrin and AP-1 are required for the formation of mucin-type secretory granules in Drosophila larval salivary gland cells. Clathrin and AP-1 colocalize with secretory cargo at the trans-Golgi network (TGN) and on immature granules. Moreover, clathrin recruitment to the TGN requires AP-1. Strikingly, loss of AP-1 or clathrin profoundly blocks granule biogenesis. Regulated secretion of hormones, digestive enzymes, and other biologically active molecules requires the formation of secretory granules. Clathrin and the clathrin adaptor protein complex 1 (AP-1) are necessary for maturation of exocrine, endocrine, and neuroendocrine secretory granules. However, the initial steps of secretory granule biogenesis are only minimally understood. Powerful genetic approaches available in the fruit fly Drosophila melanogaster were used to investigate the molecular pathway for biogenesis of the mucin-containing “glue granules” that form within epithelial cells of the third-instar larval salivary gland. Clathrin and AP-1 colocalize at the trans-Golgi network (TGN) and clathrin recruitment requires AP-1. Furthermore, clathrin and AP-1 colocalize with secretory cargo at the TGN and on immature granules. Finally, loss of clathrin or AP-1 leads to a profound block in secretory granule formation. These findings establish a novel role for AP-1– and clathrin-dependent trafficking in the biogenesis of mucin-containing secretory granules.