Borgonovo B, Racchetti G, Malosio M, Benfante R, Podini P, Rosa P, Meldolesi J
DIBIT, Department of Neurosciences, San Raffaele Scientific Institute and B. Ceccarelli Center, Department of Pharmacology, University of Milan, 20132 Milan, Italy.
J Biol Chem. 1998 Dec 25;273(52):34683-6. doi: 10.1074/jbc.273.52.34683.
Neurosecretion competence is intended as the ability of neurosecretory cells to express dense and clear vesicles discharged by regulated exocytosis (neurotransmitter release). Such a property, which so far has never been studied independently, is investigated here by a heterotypic cell fusion approach, using a clone of rat pheochromocytoma PC12 cells totally incompetent for neurosecretion that still largely maintains its typical molecular and cellular phenotype. When fused with wild-type partners of various species (rat, human) and specialization (PC12, neuroblastoma SH-SY5Y, HeLa), the defective cells reacquire their competence as revealed by the expression of their secretion-specific proteins. Fused wild-type cells therefore appear able to complement defective cells by providing them with factor(s) inducing the reactivation of their secretory program. The mechanism of action of these factors may consist not in a coordinate unblocking of transcription but in the prevention of a rapid post-transcriptional degradation of the mRNAs for secretion-specific genes.
神经分泌能力是指神经分泌细胞表达通过调节性胞吐作用释放的致密和清亮囊泡(神经递质释放)的能力。到目前为止,这种特性从未被单独研究过,本文通过异型细胞融合方法进行研究,使用完全无神经分泌能力但仍在很大程度上保持其典型分子和细胞表型的大鼠嗜铬细胞瘤PC12细胞克隆。当与各种物种(大鼠、人类)和专业化程度不同的野生型伙伴(PC12、神经母细胞瘤SH-SY5Y、HeLa)融合时,缺陷细胞通过分泌特异性蛋白的表达重新获得其能力。因此,融合的野生型细胞似乎能够通过为缺陷细胞提供诱导其分泌程序重新激活的因子来补充缺陷细胞。这些因子的作用机制可能不在于转录的协同解除阻断,而在于防止分泌特异性基因的mRNA在转录后快速降解。