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融合孔、SNARE 蛋白和胞吐作用。

Fusion pores, SNAREs, and exocytosis.

机构信息

Celica Biomedical Center, Ljubljana, Slovenia.

出版信息

Neuroscientist. 2013 Apr;19(2):160-74. doi: 10.1177/1073858412461691. Epub 2012 Sep 26.

DOI:10.1177/1073858412461691
PMID:23019088
Abstract

Exocytosis is a multistage process involving a merger between the vesicle and the plasma membranes, leading to the formation of a fusion pore, a channel, through which secretions are released from the vesicle to the cell exterior. A stimulus may influence the pore by either dilating it completely (full-fusion exocytosis) or mediating a reversible closure (transient exocytosis). In neurons, these transitions are short-lived and not accessible for experimentation. However, in some neuroendocrine cells, initial fusion pores may reopen several hundred times, indicating their stability. Moreover, these pores are too narrow to pass luminal molecules to the extracellular space, termed release-unproductive. However, on stimulation, their diameter dilates, initiating the release of cargo without de novo fusion pore formation. To explain the stability of the initial narrow fusion pores, anisotropic membrane constituents with non-axisymmetrical shape were proposed to accumulate in the fusion pore membrane. Although the nature of these is unclear, they may consist of lipids and proteins, including SNAREs, which may facilitate and regulate the pre- and post-fusional stages of exocytosis. In the future, a more detailed insight into the molecular control of fusion pore stabilization and regulation will generate a better understanding of fusion pore physiology in health and disease.

摘要

胞吐作用是一个多阶段的过程,涉及囊泡与质膜的融合,导致融合孔的形成,这是一个通道,囊泡中的分泌物通过该通道释放到细胞外。刺激可以通过完全扩张孔(完全融合胞吐作用)或介导可逆关闭(瞬时胞吐作用)来影响孔。在神经元中,这些转变是短暂的,无法进行实验。然而,在一些神经内分泌细胞中,初始融合孔可能会重新打开数百次,表明其稳定性。此外,这些孔太窄,无法将腔分子传递到细胞外空间,称为释放非产性。然而,在受到刺激时,它们的直径会扩张,在没有新的融合孔形成的情况下启动货物的释放。为了解释初始狭窄融合孔的稳定性,提出了具有非轴对称形状的各向异性膜成分在融合孔膜中积累。尽管这些成分的性质尚不清楚,但它们可能包括脂质和蛋白质,包括 SNAREs,这可能有助于和调节胞吐作用的融合前和融合后阶段。未来,对融合孔稳定和调节的分子控制有更详细的了解,将有助于更好地理解融合孔在健康和疾病中的生理学。

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