Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells
Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells
复制标题
沉默缺陷的肾上腺嗜铬细胞中大型致密核心囊泡的成熟受损
DOI：
10.1242/jcs.161414
复制
发表时间：
2015-04-01
影响因子：
4
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Hao, Zhenhua;Wei, Lisi;Li, Wei
大致密核囊泡（LDCV）是一种溶酶体相关的细胞器，在专门的分泌细胞中参与激素和神经肽的分泌。颗粒蛋白家族是LDCV生物发生的驱动力，但颗粒蛋白在这一生物发生途径中的分选机制在很大程度上是未知的。mu突变小鼠是Hermansky-Pudlak综合征的小鼠模型，其静音基因（也称为Bloc1s5）携带自发的零突变，该基因编码溶酶体相关细胞器复合物-1 （bloc1）的生物发生亚基。在这里，我们发现LDCVs在mu肾上腺染色质细胞中扩增。嗜铬粒蛋白A （Chromogranin A, CgA，也称CHGA）在肾上腺和被抑制细胞中升高。mu小鼠CgA的增加可能是由于未成熟LDCV无法输出该分子，从而损害了LDCV的成熟和对接。在嗜铬细胞中，易释放池的大小和囊泡释放频率降低。我们的研究表明，在ldcv的生物发生过程中，沉默蛋白参与了CgA的选择性输出。
ABSTRACT The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5), which encodes a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky–Pudlak syndrome. Here, we found that LDCVs were enlarged in mu adrenal chromaffin cells. Chromogranin A (CgA, also known as CHGA) was increased in mu adrenals and muted-knockdown cells. The increased CgA in mu mice was likely due a failure to export this molecule out of immature LDCVs, which impairs LDCV maturation and docking. In mu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the selective export of CgA during the biogenesis of LDCVs.