GAP-43 controls the availability of secretory chromaffin granules for regulated exocytosis by stimulating a granule-associated G0.
GAP-43 controls the availability of secretory chromaffin granules for regulated exocytosis by stimulating a granule-associated G0.
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GAP-43 通过刺激颗粒相关的 G0 来控制分泌性嗜铬颗粒的可用性，以调节胞吐作用。
DOI：
10.1016/s0021-9258(18)43811-2
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
M. Bader
中科院分区：
文献类型：
--
作者：
N. Vitale;J. Deloulme;D. Thierse;D. Aunis;M. Bader
除了在信号转导中起作用外，异源三聚体G蛋白也可能参与膜运输事件，如它们在特定细胞内隔室中的存在所表明的。在嗜铬细胞中，G α 0与分泌细胞器相关，其激活抑制胞吐作用。虽然质膜结合G蛋白被细胞表面受体激活，但控制细胞器相关G蛋白的细胞内蛋白目前尚不清楚。GAP-43是一种富含于轴突生长锥和突触前末梢的神经元蛋白，由于它可以直接刺激纯化的G 0，因此是一种可能的候选者。我们研究了肾上腺髓质GAP-43与嗜铬颗粒相关G 0的相互作用及其对儿茶酚胺分泌的影响。细胞质和depalmitoylated膜提取的GAP-43被发现刺激鸟嘌呤核苷酸的结合和交换活动的嗜铬颗粒膜。在透性化的嗜铬细胞中，两种形式的GAP-43阻断了钙依赖性胞吐作用，并且这种作用被针对G α 0的特异性抗体抑制。与G 0相互作用差距-43结构域对应的合成肽抑制儿茶酚胺分泌。这种作用可以选择性地逆转的COOH-末端肽G α 0。这些结果表明，GAP-43可能是一个内源性的假受体的分泌颗粒结合形式的G 0，从而可以控制嗜铬细胞中的钙调节胞吐。
Besides having a role in signal transduction, heterotrimeric G proteins may also be involved in membrane trafficking events as suggested by their presence in specific intracellular compartments. In chromaffin cells, G alpha 0 is associated with secretory organelles, and its activation inhibits exocytosis. Although plasma membrane-bound G proteins are activated by cell-surface receptors, the intracellular proteins controlling organelle-associated G proteins are currently unknown. GAP-43, a neuronal protein enriched in axonal growth cones and presynaptic terminals, is one possible candidate since it can directly stimulate purified G0. We have investigated the interaction of adrenal medullary GAP-43 with chromaffin granule-associated G0 and its effect on catecholamine secretion. Cytosolic and depalmitoylated membrane-extracted GAP-43 were found to stimulate guanine nucleotide binding and exchange activity in chromaffin granule membranes. In permeabilized chromaffin cells, both forms of GAP-43 blocked calcium-dependent exocytosis, and this effect was inhibited by specific antibodies against G alpha 0. A synthetic peptide corresponding to the GAP-43 domain that interacts with G0 inhibited catecholamine secretion. This effect could be selectively reversed by the COOH-terminal peptide of G alpha 0. These results indicate that GAP-43 may be an endogenous pseudoreceptor for the secretory granule-bound form of G0 and can thereby control calcium-regulated exocytosis in chromaffin cells.