Koshimizu Hisatsugu, Kim Taeyoon, Cawley Niamh X, Loh Y Peng
Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health Bethesda, MD 20892, USA.
Regul Pept. 2010 Nov 30;165(1):95-101. doi: 10.1016/j.regpep.2010.09.006. Epub 2010 Oct 13.
Chromogranin A (CgA), a member of the granin family serves several important cell biological roles in (neuro)endocrine cells which are summarized in this review. CgA is a "prohormone" that is synthesized at the rough endoplasmic reticulum and transported into the cisternae of this organelle via its signal peptide. It is then trafficked to the Golgi complex and then to the trans-Golgi network (TGN) where CgA aggregates at low pH in the presence of calcium. The CgA aggregates provide the physical driving force to induce budding of the TGN membrane resulting in dense core granule (DCG) formation. Within the granule, a small amount of the CgA is processed to bioactive peptides, including a predicted C-terminal peptide, serpinin. Upon stimulation, DCGs undergo exocytosis and CgA and its derived peptides are released. Serpinin, acting extracellularly is able to signal the increase in transcription of a serine protease inhibitor, protease nexin-1 (PN-1) that protects DCG proteins against degradation in the Golgi complex, which then enhances DCG biogenesis to replenish those that were released. Thus CgA and its derived peptide, serpinin, plays a significant role in granule formation and regulation of granule biogenesis, respectively, in (neuro) endocrine cells.
嗜铬粒蛋白A（CgA）是颗粒蛋白家族的一员，在（神经）内分泌细胞中发挥多种重要的细胞生物学作用，本综述对此进行了总结。CgA是一种“前激素”，在糙面内质网合成，并通过其信号肽转运到该细胞器的潴泡中。然后它被运输到高尔基体复合体，再到反式高尔基体网络（TGN），在那里CgA在低pH值和钙存在的情况下聚集。CgA聚集体提供物理驱动力，诱导TGN膜出芽，导致致密核心颗粒（DCG）形成。在颗粒内，少量的CgA被加工成生物活性肽，包括一种预测的C端肽——丝氨酸蛋白酶抑制素。受到刺激后，DCG发生胞吐作用，CgA及其衍生肽被释放。丝氨酸蛋白酶抑制素在细胞外发挥作用，能够发出信号，使丝氨酸蛋白酶抑制剂蛋白酶nexin-1（PN-1）的转录增加，该抑制剂可保护DCG蛋白在高尔基体复合体中不被降解，进而增强DCG生物合成，以补充那些被释放的DCG。因此，CgA及其衍生肽丝氨酸蛋白酶抑制素分别在（神经）内分泌细胞的颗粒形成和颗粒生物合成调节中发挥重要作用。
