Chock S P, Schmauder-Chock E A
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Biofactors. 1990 Jul;2(3):133-46.
By combining ultrastructural techniques with a biochemical approach to study the mechanism of mast cell stimulus-secretion coupling and by using purified secretory granules to confirm those early biochemical events which originate from within the secretory granule, a new model for the mechanism of secretory granule exocytosis has emerged. This model not only provides the mechanism by which an activated granule can achieve fusion with the plasma membrane, but it also provides the rationale for the linking of the various early biochemical events to the process of granule activation and thus to exocytosis. Although we still do not understand how the 'activating signal', which results from the stimulation of cell surface receptors, can be conveyed to the granule to cause its activation, we are certain that this 'signal' must cause an influx of water into the matrix of the target granule. This influx of water is what initiates the granule activation process. The major intragranular events which are triggered by this water influx include: (i) de novo membrane assembly; (ii) protein proteolysis; (iii) release of arachidonic acid from matrix-bound phospholipid by phospholipase A2; (iv) initiation of the arachidonic acid cascade and the synthesis of eicosanoids; (v) rapid phospholipid turnover; and (vi) the discharge of matrix materials into the cytoplasm of the activated cell via the fusion of de novo generated vesicles with the perigranular membrane. The ejection of some matrix contents which may include histamine, Ca2+, calmodulin, protease, the products of the arachidonic acid cascade and the products of phospholipid turnover into the cytosole, may serve to turn on the various metabolic machineries needed to initiate a cellular recovery phase.
通过将超微结构技术与生物化学方法相结合来研究肥大细胞刺激-分泌偶联机制，并利用纯化的分泌颗粒来证实那些源自分泌颗粒内部的早期生物化学事件，一种分泌颗粒胞吐作用机制的新模型应运而生。该模型不仅提供了活化颗粒与质膜实现融合的机制，还为将各种早期生物化学事件与颗粒活化过程进而与胞吐作用联系起来提供了理论依据。尽管我们仍不明白由细胞表面受体刺激产生的“激活信号”如何传递至颗粒以使其活化，但我们确定该“信号”必定会导致水流入目标颗粒的基质中。这种水的流入正是启动颗粒活化过程的因素。由这种水流入引发的主要颗粒内事件包括：（i）从头组装膜；（ii）蛋白质水解；（iii）磷脂酶A2从与基质结合的磷脂中释放花生四烯酸；（iv）启动花生四烯酸级联反应并合成类二十烷酸；（v）快速的磷脂周转；以及（vi）通过新生成的小泡与颗粒周围膜的融合将基质物质排放到活化细胞的细胞质中。一些基质成分（可能包括组胺、Ca2+、钙调蛋白、蛋白酶、花生四烯酸级联反应的产物以及磷脂周转的产物）排入细胞质，可能有助于开启启动细胞恢复阶段所需的各种代谢机制。
