Regulation of fusion pore closure and compound exocytosis in neuroendocrine PC12 cells by SCAMP1.
Regulation of fusion pore closure and compound exocytosis in neuroendocrine PC12 cells by SCAMP1.
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DOI：
10.1111/j.1600-0854.2011.01170.x
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Castle D
中科院分区：
文献类型：
--
作者：
Zhang J;Castle D
在胞吐过程中，神经内分泌细胞可以通过直接在融合位点偶联内吞作用而实现从致密核心囊泡（DCV）中部分释放储存的分泌产物，而不完全释放。部分分泌的生理作用是实质性的兴趣。关于SNARE介导的胞吐起始和动力蛋白介导的胞吞完成，我们知道得很多，但关于偶联事件知之甚少。我们已经使用实时显微镜检查分泌载体膜蛋白SCAMP 1在PC 12细胞中的外吞-内吞偶联中的作用。虽然已知SCAMP 1表达减少会在DCV胞吐作用开始期间阻碍新打开的融合孔的扩张，但我们现在表明SCAMP 1缺乏也会抑制融合孔在打开后的闭合。抑制导致融合图在质膜上积累。通过恢复表达恢复闭合，并通过过表达略微加速闭合。有趣的是，SCAMP 1缺失导致的孔闭合抑制似乎增加了DCV与已经融合的DCV的二次融合（复合胞吐）。出乎意料的是，在SCAMP 1缺陷型细胞中，化合物胞吐作用后扩展的DCV膜的再内化似乎正常进行。SCAMP 1在促进融合孔的扩张和闭合中的明显双重作用暗示了其在外吞-内吞偶联和调节部分分泌中的功能。其次，SCAMP 1可用于限制复合胞吐的程度。
During exocytosis, neuroendocrine cells can achieve partial release of stored secretory products from dense core vesicles (DCVs) by coupling endocytosis directly at fusion sites and without full discharge. The physiological role of partial secretion is of substantial interest. Much is known about SNARE-mediated initiation of exocytosis and dynamin-mediated completion of endocytosis, but little is known about coupling events. We have used real-time microscopy to examine the role of secretory carrier membrane protein SCAMP1 in exo-endocytic coupling in PC12 cells. While reduced SCAMP1 expression is known to impede dilation of newly opened fusion pores during onset of DCV exocytosis, we now show that SCAMP1 deficiency also inhibits closure of fusion pores after they have opened. Inhibition causes accumulation of fusion figures at the plasma membrane. Closure is recovered by restoring expression and accelerated slightly by overexpression. Interestingly, inhibited pore closure resulting from loss of SCAMP1 appears to increase secondary fusion of DCVs to already-fused DCVs (compound exocytosis). Unexpectedly, reinternalization of expanded DCV membranes following compound exocytosis appears to proceed normally in SCAMP1-deficient cells. SCAMP1’s apparent dual role in facilitating dilation and closure of fusion pores implicates its function in exo-endocytic coupling and in the regulation of partial secretion. Secondarily, SCAMP1 may serve to limit the extent of compound exocytosis.
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影响因子：
3.3
作者：
Hubbard, C;Singleton, D;Castle, D
通讯作者：
Castle, D
影响因子：
3.4
作者：
Ellena, JF;Moulthrop, J;Cafiso, DS
通讯作者：
Cafiso, DS
影响因子：
5.3
作者：
Elhamdani, A;Azizi, F;Artalejo, CR
通讯作者：
Artalejo, CR
影响因子：
3.3
作者：
Liu, LX;Guo, ZH;Castle, D
通讯作者：
Castle, D
DOI：
10.1073/pnas.012607799
发表时间：
2002-01-08
影响因子：
11.1
作者：
Lee, E;De Camilli, P
通讯作者：
De Camilli, P