Regulation of Constitutive Exocytic Transport by Membrane Receptors

Regulation of Constitutive Exocytic Transport by Membrane Receptors
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膜受体对组成型胞吐运输的调节

DOI:
--
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发表时间:
1996
影响因子:
4.8
通讯作者:
M. D. De Matteis
M. D. De Matteis
中科院分区:
生物学2区
文献类型:
--
作者:
R. Buccione;S. Bannykh;I. Santone;M. Baldassarre;F. Facchiano;Y. Bozzi;G. di Tullio;A. Mironov;A. Luini;M. D. De Matteis

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结合生化和形态测量方法来检查组成型分泌转运是否可能由质膜受体控制,因为这种可能性将具有重大的生理意义。事实上,大鼠嗜碱性白血病细胞中的 IgE 受体刺激有效地增加了可溶性脉冲标记的 S-硫酸化糖胺聚糖从远端高尔基体运输到细胞表面的速率。这种效应很大程度上依赖于蛋白激酶 C (PKC)。 PKC 的直接激活也刺激了糖胺聚糖的组成型运输,正如使用激动性和拮抗性 PKC 配体所表明的那样。 PKC 配体对膜结合蛋白(水泡性口炎病毒糖蛋白)从远端高尔基体到质膜的胞吐转运也具有有效但不同的影响,激活剂会轻微刺激该蛋白,而 PKC 抑制剂会严重抑制该蛋白。形态学分析显示,分泌途径的细胞器响应 IgE 受体刺激和直接 PKC 激活而发生显着变化(源自内质网和高尔基体的芽和囊泡数量增加,高尔基体区室的表面积和体积增加),表明胞吐运动的全面激活。这些结果表明,膜受体(以及直接 PKC 刺激)可以诱导组成性运输通量和胞吐器形态的快速而大的变化。
Biochemical and morphometric approaches were combined to examine whether constitutive secretory transport might be controlled by plasma membrane receptors, as this possibility would have significant physiological implications. Indeed, IgE receptor stimulation in rat basophilic leukemia cells potently increased the rate of transport of soluble pulse-labeled S-sulfated glycosaminoglycans from distal Golgi compartments to the cell surface. This effect was largely protein kinase C (PKC)-dependent. Direct activation of PKC also stimulated constitutive transport of glycosaminoglycans, as indicated by the use of agonistic and antagonistic PKC ligands. PKC ligands also had potent, but different, effects on the exocytic transport from distal Golgi compartments to the plasma membrane of a membrane-bound protein (vesicular stomatitis virus glycoprotein), which was slightly stimulated by activators and profoundly suppressed by inhibitors of PKC. Morphological analysis showed impressive changes of the organelles of the secretory pathway in response to IgE receptor stimulation and to direct PKC activation (enhanced number of buds and vesicles originating from the endoplasmic reticulum and Golgi and increase in surface and volume of Golgi compartments), suggestive of an overall activation of exocytic movements. These results show that rapid and large changes in constitutive transport fluxes and in the morphology of the exocytic apparatus can be induced by membrane receptors (as well as by direct PKC stimulation).
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